Midazolam Pharmacokinetics in Morbidly Obese Patients Following Semi-Simultaneous Oral and Intravenous Administration: A Comparison with Healthy Volunteers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-10

AUTHORS

Margreke J. E. Brill, Anne van Rongen, Aletta P. I. Houwink, Jacobus Burggraaf, Bert van Ramshorst, René J. Wiezer, Eric P. A. van Dongen, Catherijne A. J. Knibbe

ABSTRACT

BACKGROUND: While in vitro and animal studies have shown reduced cytochrome P450 (CYP) 3A activity due to obesity, clinical studies in (morbidly) obese patients are scarce. As CYP3A activity may influence both clearance and oral bioavailability in a distinct manner, in this study the pharmacokinetics of the CYP3A substrate midazolam were evaluated after semi-simultaneous oral and intravenous administration in morbidly obese patients, and compared with healthy volunteers. METHODS: Twenty morbidly obese patients [mean body weight 144 kg (range 112-186 kg) and mean body mass index 47 kg/m(2) (range 40-68 kg/m(2))] participated in the study. All patients received a midazolam 7.5 mg oral and 5 mg intravenous dose (separated by 159 ± 67 min) and per patient 22 samples over 11 h were collected. Data from 12 healthy volunteers were available for a population pharmacokinetic analysis using NONMEM(®). RESULTS: In the three-compartment model in which oral absorption was characterized by a transit absorption model, population mean clearance (relative standard error %) was similar [0.36 (4 %) L/min], while oral bioavailability was 60 % (13 %) in morbidly obese patients versus 28 % (7 %) in healthy volunteers (P < 0.001). Central and peripheral volumes of distribution increased substantially with body weight (both P < 0.001) and absorption rate (transit rate constant) was lower in morbidly obese patients [0.057 (5 %) vs. 0.130 (14 %) min(-1), P < 0.001]. CONCLUSIONS: In morbidly obese patients, systemic clearance of midazolam is unchanged, while oral bioavailability is increased. Given the large increase in volumes of distribution, dose adaptations for intravenous midazolam should be considered. Further research should elucidate the exact physiological changes at intestinal and hepatic level contributing to these findings. More... »

PAGES

931-941

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s40262-014-0166-x

DOI

http://dx.doi.org/10.1007/s40262-014-0166-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023353991

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25141974


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1116", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical Physiology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Administration, Intravenous", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Administration, Oral", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adolescent", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adult", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Biological Availability", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Case-Control Studies", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Healthy Volunteers", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hypnotics and Sedatives", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Midazolam", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Middle Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Models, Biological", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Obesity, Morbid", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Prospective Studies", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Time Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Young Adult", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "St. Antonius Ziekenhuis", 
          "id": "https://www.grid.ac/institutes/grid.415960.f", 
          "name": [
            "Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands", 
            "Department of Clinical Pharmacy, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Brill", 
        "givenName": "Margreke J. E.", 
        "id": "sg:person.01136601371.53", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01136601371.53"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Antonius Ziekenhuis", 
          "id": "https://www.grid.ac/institutes/grid.415960.f", 
          "name": [
            "Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands", 
            "Department of Clinical Pharmacy, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "van Rongen", 
        "givenName": "Anne", 
        "id": "sg:person.01253027771.31", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01253027771.31"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Antonius Ziekenhuis", 
          "id": "https://www.grid.ac/institutes/grid.415960.f", 
          "name": [
            "Department of Anaesthesiology, Intensive Care and Pain Management, St. Antonius Hospital, Nieuwegein, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Houwink", 
        "givenName": "Aletta P. I.", 
        "id": "sg:person.0776526172.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0776526172.41"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Centre for Human Drug Research", 
          "id": "https://www.grid.ac/institutes/grid.418011.d", 
          "name": [
            "Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands", 
            "Centre for Human Drug Research (CHDR), Leiden, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Burggraaf", 
        "givenName": "Jacobus", 
        "id": "sg:person.01336243554.64", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01336243554.64"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Antonius Ziekenhuis", 
          "id": "https://www.grid.ac/institutes/grid.415960.f", 
          "name": [
            "Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "van Ramshorst", 
        "givenName": "Bert", 
        "id": "sg:person.0756446730.73", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0756446730.73"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Antonius Ziekenhuis", 
          "id": "https://www.grid.ac/institutes/grid.415960.f", 
          "name": [
            "Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wiezer", 
        "givenName": "Ren\u00e9 J.", 
        "id": "sg:person.01155275674.37", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01155275674.37"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Antonius Ziekenhuis", 
          "id": "https://www.grid.ac/institutes/grid.415960.f", 
          "name": [
            "Department of Anaesthesiology, Intensive Care and Pain Management, St. Antonius Hospital, Nieuwegein, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "van Dongen", 
        "givenName": "Eric P. A.", 
        "id": "sg:person.01236550053.11", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01236550053.11"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St. Antonius Ziekenhuis", 
          "id": "https://www.grid.ac/institutes/grid.415960.f", 
          "name": [
            "Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands", 
            "Department of Clinical Pharmacy, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Knibbe", 
        "givenName": "Catherijne A. J.", 
        "id": "sg:person.012736105417.27", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012736105417.27"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/clpt.1992.54", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000324302", 
          "https://doi.org/10.1038/clpt.1992.54"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1381/096089203322190853", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003544977", 
          "https://doi.org/10.1381/096089203322190853"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/clpt.2009.311", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003683276", 
          "https://doi.org/10.1038/clpt.2009.311"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00003088-200544100-00004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003951240", 
          "https://doi.org/10.2165/00003088-200544100-00004"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00003088-200544100-00004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003951240", 
          "https://doi.org/10.2165/00003088-200544100-00004"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/11599410-000000000-00000", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004003598", 
          "https://doi.org/10.2165/11599410-000000000-00000"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci25102", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004145275"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/dme.12360", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004301534"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s11095-006-9067-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007463799", 
          "https://doi.org/10.1007/s11095-006-9067-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00000542-198407000-00006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009301650"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00000542-198407000-00006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009301650"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.lfs.2011.05.005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009481659"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-06-0023", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010686656"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0002-9343(83)91071-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010730797"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s11095-006-0071-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011164523", 
          "https://doi.org/10.1007/s11095-006-0071-6"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1067/mcp.2002.129068", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011988694", 
          "https://doi.org/10.1067/mcp.2002.129068"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/clpt.1992.136", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013103365", 
          "https://doi.org/10.1038/clpt.1992.136"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev.pharmtox.46.120604.141059", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014053236"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev.pharmtox.46.120604.141059", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014053236"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ijo.2012.159", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018366106", 
          "https://doi.org/10.1038/ijo.2012.159"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2125.2005.02389.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019539043"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2125.2005.02389.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019539043"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/clpt.2012.261", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020874304", 
          "https://doi.org/10.1038/clpt.2012.261"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf01063554", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021373991", 
          "https://doi.org/10.1007/bf01063554"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1023/a:1015939917646", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022244764", 
          "https://doi.org/10.1023/a:1015939917646"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10928-007-9066-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023254119", 
          "https://doi.org/10.1007/s10928-007-9066-0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2362.2003.01154.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024326295"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1381/096089206777346682", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025990405", 
          "https://doi.org/10.1381/096089206777346682"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.pharmthera.2012.12.007", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026929795"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1096/fj.02-0195fje", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027353228"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1208/s12248-010-9212-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031045356", 
          "https://doi.org/10.1208/s12248-010-9212-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.2165/00003088-198409020-00005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031092720", 
          "https://doi.org/10.2165/00003088-198409020-00005"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/dmd.109.027466", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033292654"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1208/s12248-009-9099-y", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034493508", 
          "https://doi.org/10.1208/s12248-009-9099-y"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/jhep.2002.33215", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037448276"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.clnu.2012.02.009", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039378225"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/j.1552-4604.1983.tb02750.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042878512"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000318741", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044091234"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cgh.2006.12.021", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044572038"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.toxlet.2010.06.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045245431"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf00562804", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048517022", 
          "https://doi.org/10.1007/bf00562804"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf00562804", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048517022", 
          "https://doi.org/10.1007/bf00562804"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf00562804", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048517022", 
          "https://doi.org/10.1007/bf00562804"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2044.1987.tb03086.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048949424"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jaci.2005.02.023", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053670910"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00008571-200004000-00001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060289721"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00008571-200004000-00001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060289721"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00008571-200004000-00001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060289721"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00008571-200004000-00001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060289721"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pcc.0b013e3181fe406d", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060343647"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pcc.0b013e3181fe406d", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060343647"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pcc.0b013e3181fe406d", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060343647"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci200525102", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063416820"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/1389200043335559", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069175464"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/138920007782109733", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069175656"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074253403", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1076189439", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1078566769", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2014-10", 
    "datePublishedReg": "2014-10-01", 
    "description": "BACKGROUND: While in vitro and animal studies have shown reduced cytochrome P450 (CYP) 3A activity due to obesity, clinical studies in (morbidly) obese patients are scarce. As CYP3A activity may influence both clearance and oral bioavailability in a distinct manner, in this study the pharmacokinetics of the CYP3A substrate midazolam were evaluated after semi-simultaneous oral and intravenous administration in morbidly obese patients, and compared with healthy volunteers.\nMETHODS: Twenty morbidly obese patients [mean body weight 144\u00a0kg (range 112-186\u00a0kg) and mean body mass index 47\u00a0kg/m(2) (range 40-68\u00a0kg/m(2))] participated in the study. All patients received a midazolam 7.5\u00a0mg oral and 5\u00a0mg intravenous dose (separated by 159\u00a0\u00b1\u00a067\u00a0min) and per patient 22 samples over 11\u00a0h were collected. Data from 12 healthy volunteers were available for a population pharmacokinetic analysis using NONMEM(\u00ae).\nRESULTS: In the three-compartment model in which oral absorption was characterized by a transit absorption model, population mean clearance (relative standard error %) was similar [0.36 (4\u00a0%)\u00a0L/min], while oral bioavailability was 60\u00a0% (13\u00a0%) in morbidly obese patients versus 28\u00a0% (7\u00a0%) in healthy volunteers (P\u00a0<\u00a00.001). Central and peripheral volumes of distribution increased substantially with body weight (both P\u00a0<\u00a00.001) and absorption rate (transit rate constant) was lower in morbidly obese patients [0.057 (5\u00a0%) vs. 0.130 (14\u00a0%)\u00a0min(-1), P\u00a0<\u00a00.001].\nCONCLUSIONS: In morbidly obese patients, systemic clearance of midazolam is unchanged, while oral bioavailability is increased. Given the large increase in volumes of distribution, dose adaptations for intravenous midazolam should be considered. Further research should elucidate the exact physiological changes at intestinal and hepatic level contributing to these findings.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1007/s40262-014-0166-x", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1085321", 
        "issn": [
          "0312-5963", 
          "1179-1926"
        ], 
        "name": "Clinical Pharmacokinetics", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "10", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "53"
      }
    ], 
    "name": "Midazolam Pharmacokinetics in Morbidly Obese Patients Following Semi-Simultaneous Oral and Intravenous Administration: A Comparison with Healthy Volunteers", 
    "pagination": "931-941", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "6f43d80b3199382ee81b0d926471a9bba371f14f1094d1f1a2998e4ac6a48500"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "25141974"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "7606849"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s40262-014-0166-x"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1023353991"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s40262-014-0166-x", 
      "https://app.dimensions.ai/details/publication/pub.1023353991"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T09:55", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000347_0000000347/records_89801_00000001.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1007%2Fs40262-014-0166-x"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s40262-014-0166-x'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s40262-014-0166-x'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s40262-014-0166-x'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s40262-014-0166-x'


 

This table displays all metadata directly associated to this object as RDF triples.

354 TRIPLES      21 PREDICATES      94 URIs      39 LITERALS      27 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s40262-014-0166-x schema:about N123315936be1429d8fd38d66466cf6c2
2 N149b0e34b34146d8a8ed679fbec18677
3 N2687c6fadad6427e94079b41ddf19f5d
4 N35671f17e4ba4f938b84d371d29721f5
5 N4bf16160b05c407abf50f3198edd3fc5
6 N4d80d3441cd9409280209ad4792809c7
7 N64e875da8e6f41d0909c690b5a08d052
8 N78e327a05ab5454c8a19e2db22759b5a
9 N93d75e3eec114febad35ee7645b4dcfc
10 Na728309202014cd3bde9585773e0fb8b
11 Nc3248f3cd13243e58ec81d29d521ee71
12 Ncdb9fdf03f654e258bf192b7249af49c
13 Nd1cc4a3f43114bee9f3197f3d38f1d56
14 Nd35f6a9de00b4de48958c99af129413b
15 Ne776f2edf52a48cf9bf41e6526c51562
16 Nec8fc18c7a364edaa614609bc7406cec
17 Nee957029271d408c8697c02a13ceb3bb
18 Nfed81f66f15945218bb2bb717daadaf6
19 anzsrc-for:11
20 anzsrc-for:1116
21 schema:author Nfb22533cc1334931bfbad385922f1374
22 schema:citation sg:pub.10.1007/bf00562804
23 sg:pub.10.1007/bf01063554
24 sg:pub.10.1007/s10928-007-9066-0
25 sg:pub.10.1007/s11095-006-0071-6
26 sg:pub.10.1007/s11095-006-9067-5
27 sg:pub.10.1023/a:1015939917646
28 sg:pub.10.1038/clpt.1992.136
29 sg:pub.10.1038/clpt.1992.54
30 sg:pub.10.1038/clpt.2009.311
31 sg:pub.10.1038/clpt.2012.261
32 sg:pub.10.1038/ijo.2012.159
33 sg:pub.10.1067/mcp.2002.129068
34 sg:pub.10.1208/s12248-009-9099-y
35 sg:pub.10.1208/s12248-010-9212-2
36 sg:pub.10.1381/096089203322190853
37 sg:pub.10.1381/096089206777346682
38 sg:pub.10.2165/00003088-198409020-00005
39 sg:pub.10.2165/00003088-200544100-00004
40 sg:pub.10.2165/11599410-000000000-00000
41 https://app.dimensions.ai/details/publication/pub.1074253403
42 https://app.dimensions.ai/details/publication/pub.1076189439
43 https://app.dimensions.ai/details/publication/pub.1078566769
44 https://doi.org/10.1002/j.1552-4604.1983.tb02750.x
45 https://doi.org/10.1016/0002-9343(83)91071-9
46 https://doi.org/10.1016/j.cgh.2006.12.021
47 https://doi.org/10.1016/j.clnu.2012.02.009
48 https://doi.org/10.1016/j.jaci.2005.02.023
49 https://doi.org/10.1016/j.lfs.2011.05.005
50 https://doi.org/10.1016/j.pharmthera.2012.12.007
51 https://doi.org/10.1016/j.toxlet.2010.06.003
52 https://doi.org/10.1046/j.1365-2362.2003.01154.x
53 https://doi.org/10.1053/jhep.2002.33215
54 https://doi.org/10.1096/fj.02-0195fje
55 https://doi.org/10.1097/00000542-198407000-00006
56 https://doi.org/10.1097/00008571-200004000-00001
57 https://doi.org/10.1097/pcc.0b013e3181fe406d
58 https://doi.org/10.1111/dme.12360
59 https://doi.org/10.1111/j.1365-2044.1987.tb03086.x
60 https://doi.org/10.1111/j.1365-2125.2005.02389.x
61 https://doi.org/10.1124/dmd.109.027466
62 https://doi.org/10.1146/annurev.pharmtox.46.120604.141059
63 https://doi.org/10.1158/1078-0432.ccr-06-0023
64 https://doi.org/10.1159/000318741
65 https://doi.org/10.1172/jci200525102
66 https://doi.org/10.1172/jci25102
67 https://doi.org/10.2174/1389200043335559
68 https://doi.org/10.2174/138920007782109733
69 schema:datePublished 2014-10
70 schema:datePublishedReg 2014-10-01
71 schema:description BACKGROUND: While in vitro and animal studies have shown reduced cytochrome P450 (CYP) 3A activity due to obesity, clinical studies in (morbidly) obese patients are scarce. As CYP3A activity may influence both clearance and oral bioavailability in a distinct manner, in this study the pharmacokinetics of the CYP3A substrate midazolam were evaluated after semi-simultaneous oral and intravenous administration in morbidly obese patients, and compared with healthy volunteers. METHODS: Twenty morbidly obese patients [mean body weight 144 kg (range 112-186 kg) and mean body mass index 47 kg/m(2) (range 40-68 kg/m(2))] participated in the study. All patients received a midazolam 7.5 mg oral and 5 mg intravenous dose (separated by 159 ± 67 min) and per patient 22 samples over 11 h were collected. Data from 12 healthy volunteers were available for a population pharmacokinetic analysis using NONMEM(®). RESULTS: In the three-compartment model in which oral absorption was characterized by a transit absorption model, population mean clearance (relative standard error %) was similar [0.36 (4 %) L/min], while oral bioavailability was 60 % (13 %) in morbidly obese patients versus 28 % (7 %) in healthy volunteers (P < 0.001). Central and peripheral volumes of distribution increased substantially with body weight (both P < 0.001) and absorption rate (transit rate constant) was lower in morbidly obese patients [0.057 (5 %) vs. 0.130 (14 %) min(-1), P < 0.001]. CONCLUSIONS: In morbidly obese patients, systemic clearance of midazolam is unchanged, while oral bioavailability is increased. Given the large increase in volumes of distribution, dose adaptations for intravenous midazolam should be considered. Further research should elucidate the exact physiological changes at intestinal and hepatic level contributing to these findings.
72 schema:genre research_article
73 schema:inLanguage en
74 schema:isAccessibleForFree true
75 schema:isPartOf N94dbe82d6a514d1c947e38596fcb1033
76 Nd0899225099047189583bec124f31f1b
77 sg:journal.1085321
78 schema:name Midazolam Pharmacokinetics in Morbidly Obese Patients Following Semi-Simultaneous Oral and Intravenous Administration: A Comparison with Healthy Volunteers
79 schema:pagination 931-941
80 schema:productId N1f360030ffa54dd999773c9a60f75174
81 N28adaae4cd014f989487dafd3c17b410
82 N3e1480035f7b4cc387cce2e0eb6c56e1
83 N6c57dfedb826442398f46da4a63475b0
84 Nda1bee31b2534397b13fcbb5b77d2932
85 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023353991
86 https://doi.org/10.1007/s40262-014-0166-x
87 schema:sdDatePublished 2019-04-11T09:55
88 schema:sdLicense https://scigraph.springernature.com/explorer/license/
89 schema:sdPublisher Nac5da38948aa423fbcebf0f39be870b3
90 schema:url https://link.springer.com/10.1007%2Fs40262-014-0166-x
91 sgo:license sg:explorer/license/
92 sgo:sdDataset articles
93 rdf:type schema:ScholarlyArticle
94 N0b0b51e678ee4122b1519d05a31eea0d rdf:first sg:person.01253027771.31
95 rdf:rest N4b4f9554a6da47f6af02eaa7dde74f90
96 N123315936be1429d8fd38d66466cf6c2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
97 schema:name Hypnotics and Sedatives
98 rdf:type schema:DefinedTerm
99 N149b0e34b34146d8a8ed679fbec18677 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
100 schema:name Case-Control Studies
101 rdf:type schema:DefinedTerm
102 N1f360030ffa54dd999773c9a60f75174 schema:name pubmed_id
103 schema:value 25141974
104 rdf:type schema:PropertyValue
105 N2687c6fadad6427e94079b41ddf19f5d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
106 schema:name Healthy Volunteers
107 rdf:type schema:DefinedTerm
108 N28adaae4cd014f989487dafd3c17b410 schema:name nlm_unique_id
109 schema:value 7606849
110 rdf:type schema:PropertyValue
111 N35671f17e4ba4f938b84d371d29721f5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
112 schema:name Young Adult
113 rdf:type schema:DefinedTerm
114 N3e1480035f7b4cc387cce2e0eb6c56e1 schema:name readcube_id
115 schema:value 6f43d80b3199382ee81b0d926471a9bba371f14f1094d1f1a2998e4ac6a48500
116 rdf:type schema:PropertyValue
117 N4b4f9554a6da47f6af02eaa7dde74f90 rdf:first sg:person.0776526172.41
118 rdf:rest Nd419043ea365488191c5ddbd5dc3e985
119 N4bf16160b05c407abf50f3198edd3fc5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
120 schema:name Models, Biological
121 rdf:type schema:DefinedTerm
122 N4d80d3441cd9409280209ad4792809c7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
123 schema:name Humans
124 rdf:type schema:DefinedTerm
125 N4e225209eb2d40c7aa7e24669f70c97a rdf:first sg:person.01155275674.37
126 rdf:rest Nb30530dc65d84b92a33775d7c4f12ef7
127 N64e875da8e6f41d0909c690b5a08d052 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name Female
129 rdf:type schema:DefinedTerm
130 N6c57dfedb826442398f46da4a63475b0 schema:name doi
131 schema:value 10.1007/s40262-014-0166-x
132 rdf:type schema:PropertyValue
133 N78e327a05ab5454c8a19e2db22759b5a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
134 schema:name Time Factors
135 rdf:type schema:DefinedTerm
136 N912fcd3e567d4e82a691cdbb1e124223 rdf:first sg:person.012736105417.27
137 rdf:rest rdf:nil
138 N93d75e3eec114febad35ee7645b4dcfc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
139 schema:name Midazolam
140 rdf:type schema:DefinedTerm
141 N94dbe82d6a514d1c947e38596fcb1033 schema:issueNumber 10
142 rdf:type schema:PublicationIssue
143 Na728309202014cd3bde9585773e0fb8b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
144 schema:name Adolescent
145 rdf:type schema:DefinedTerm
146 Nac5da38948aa423fbcebf0f39be870b3 schema:name Springer Nature - SN SciGraph project
147 rdf:type schema:Organization
148 Nb30530dc65d84b92a33775d7c4f12ef7 rdf:first sg:person.01236550053.11
149 rdf:rest N912fcd3e567d4e82a691cdbb1e124223
150 Nc3248f3cd13243e58ec81d29d521ee71 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
151 schema:name Obesity, Morbid
152 rdf:type schema:DefinedTerm
153 Ncdb9fdf03f654e258bf192b7249af49c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
154 schema:name Prospective Studies
155 rdf:type schema:DefinedTerm
156 Nd0899225099047189583bec124f31f1b schema:volumeNumber 53
157 rdf:type schema:PublicationVolume
158 Nd1cc4a3f43114bee9f3197f3d38f1d56 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
159 schema:name Biological Availability
160 rdf:type schema:DefinedTerm
161 Nd35f6a9de00b4de48958c99af129413b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
162 schema:name Middle Aged
163 rdf:type schema:DefinedTerm
164 Nd419043ea365488191c5ddbd5dc3e985 rdf:first sg:person.01336243554.64
165 rdf:rest Nf68bde4baf7e4d1b90fe38310b6be2f2
166 Nda1bee31b2534397b13fcbb5b77d2932 schema:name dimensions_id
167 schema:value pub.1023353991
168 rdf:type schema:PropertyValue
169 Ne776f2edf52a48cf9bf41e6526c51562 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
170 schema:name Administration, Oral
171 rdf:type schema:DefinedTerm
172 Nec8fc18c7a364edaa614609bc7406cec schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
173 schema:name Administration, Intravenous
174 rdf:type schema:DefinedTerm
175 Nee957029271d408c8697c02a13ceb3bb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
176 schema:name Male
177 rdf:type schema:DefinedTerm
178 Nf68bde4baf7e4d1b90fe38310b6be2f2 rdf:first sg:person.0756446730.73
179 rdf:rest N4e225209eb2d40c7aa7e24669f70c97a
180 Nfb22533cc1334931bfbad385922f1374 rdf:first sg:person.01136601371.53
181 rdf:rest N0b0b51e678ee4122b1519d05a31eea0d
182 Nfed81f66f15945218bb2bb717daadaf6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
183 schema:name Adult
184 rdf:type schema:DefinedTerm
185 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
186 schema:name Medical and Health Sciences
187 rdf:type schema:DefinedTerm
188 anzsrc-for:1116 schema:inDefinedTermSet anzsrc-for:
189 schema:name Medical Physiology
190 rdf:type schema:DefinedTerm
191 sg:journal.1085321 schema:issn 0312-5963
192 1179-1926
193 schema:name Clinical Pharmacokinetics
194 rdf:type schema:Periodical
195 sg:person.01136601371.53 schema:affiliation https://www.grid.ac/institutes/grid.415960.f
196 schema:familyName Brill
197 schema:givenName Margreke J. E.
198 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01136601371.53
199 rdf:type schema:Person
200 sg:person.01155275674.37 schema:affiliation https://www.grid.ac/institutes/grid.415960.f
201 schema:familyName Wiezer
202 schema:givenName René J.
203 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01155275674.37
204 rdf:type schema:Person
205 sg:person.01236550053.11 schema:affiliation https://www.grid.ac/institutes/grid.415960.f
206 schema:familyName van Dongen
207 schema:givenName Eric P. A.
208 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01236550053.11
209 rdf:type schema:Person
210 sg:person.01253027771.31 schema:affiliation https://www.grid.ac/institutes/grid.415960.f
211 schema:familyName van Rongen
212 schema:givenName Anne
213 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01253027771.31
214 rdf:type schema:Person
215 sg:person.012736105417.27 schema:affiliation https://www.grid.ac/institutes/grid.415960.f
216 schema:familyName Knibbe
217 schema:givenName Catherijne A. J.
218 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012736105417.27
219 rdf:type schema:Person
220 sg:person.01336243554.64 schema:affiliation https://www.grid.ac/institutes/grid.418011.d
221 schema:familyName Burggraaf
222 schema:givenName Jacobus
223 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01336243554.64
224 rdf:type schema:Person
225 sg:person.0756446730.73 schema:affiliation https://www.grid.ac/institutes/grid.415960.f
226 schema:familyName van Ramshorst
227 schema:givenName Bert
228 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0756446730.73
229 rdf:type schema:Person
230 sg:person.0776526172.41 schema:affiliation https://www.grid.ac/institutes/grid.415960.f
231 schema:familyName Houwink
232 schema:givenName Aletta P. I.
233 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0776526172.41
234 rdf:type schema:Person
235 sg:pub.10.1007/bf00562804 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048517022
236 https://doi.org/10.1007/bf00562804
237 rdf:type schema:CreativeWork
238 sg:pub.10.1007/bf01063554 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021373991
239 https://doi.org/10.1007/bf01063554
240 rdf:type schema:CreativeWork
241 sg:pub.10.1007/s10928-007-9066-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023254119
242 https://doi.org/10.1007/s10928-007-9066-0
243 rdf:type schema:CreativeWork
244 sg:pub.10.1007/s11095-006-0071-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011164523
245 https://doi.org/10.1007/s11095-006-0071-6
246 rdf:type schema:CreativeWork
247 sg:pub.10.1007/s11095-006-9067-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007463799
248 https://doi.org/10.1007/s11095-006-9067-5
249 rdf:type schema:CreativeWork
250 sg:pub.10.1023/a:1015939917646 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022244764
251 https://doi.org/10.1023/a:1015939917646
252 rdf:type schema:CreativeWork
253 sg:pub.10.1038/clpt.1992.136 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013103365
254 https://doi.org/10.1038/clpt.1992.136
255 rdf:type schema:CreativeWork
256 sg:pub.10.1038/clpt.1992.54 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000324302
257 https://doi.org/10.1038/clpt.1992.54
258 rdf:type schema:CreativeWork
259 sg:pub.10.1038/clpt.2009.311 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003683276
260 https://doi.org/10.1038/clpt.2009.311
261 rdf:type schema:CreativeWork
262 sg:pub.10.1038/clpt.2012.261 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020874304
263 https://doi.org/10.1038/clpt.2012.261
264 rdf:type schema:CreativeWork
265 sg:pub.10.1038/ijo.2012.159 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018366106
266 https://doi.org/10.1038/ijo.2012.159
267 rdf:type schema:CreativeWork
268 sg:pub.10.1067/mcp.2002.129068 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011988694
269 https://doi.org/10.1067/mcp.2002.129068
270 rdf:type schema:CreativeWork
271 sg:pub.10.1208/s12248-009-9099-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1034493508
272 https://doi.org/10.1208/s12248-009-9099-y
273 rdf:type schema:CreativeWork
274 sg:pub.10.1208/s12248-010-9212-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031045356
275 https://doi.org/10.1208/s12248-010-9212-2
276 rdf:type schema:CreativeWork
277 sg:pub.10.1381/096089203322190853 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003544977
278 https://doi.org/10.1381/096089203322190853
279 rdf:type schema:CreativeWork
280 sg:pub.10.1381/096089206777346682 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025990405
281 https://doi.org/10.1381/096089206777346682
282 rdf:type schema:CreativeWork
283 sg:pub.10.2165/00003088-198409020-00005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031092720
284 https://doi.org/10.2165/00003088-198409020-00005
285 rdf:type schema:CreativeWork
286 sg:pub.10.2165/00003088-200544100-00004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003951240
287 https://doi.org/10.2165/00003088-200544100-00004
288 rdf:type schema:CreativeWork
289 sg:pub.10.2165/11599410-000000000-00000 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004003598
290 https://doi.org/10.2165/11599410-000000000-00000
291 rdf:type schema:CreativeWork
292 https://app.dimensions.ai/details/publication/pub.1074253403 schema:CreativeWork
293 https://app.dimensions.ai/details/publication/pub.1076189439 schema:CreativeWork
294 https://app.dimensions.ai/details/publication/pub.1078566769 schema:CreativeWork
295 https://doi.org/10.1002/j.1552-4604.1983.tb02750.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1042878512
296 rdf:type schema:CreativeWork
297 https://doi.org/10.1016/0002-9343(83)91071-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010730797
298 rdf:type schema:CreativeWork
299 https://doi.org/10.1016/j.cgh.2006.12.021 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044572038
300 rdf:type schema:CreativeWork
301 https://doi.org/10.1016/j.clnu.2012.02.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039378225
302 rdf:type schema:CreativeWork
303 https://doi.org/10.1016/j.jaci.2005.02.023 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053670910
304 rdf:type schema:CreativeWork
305 https://doi.org/10.1016/j.lfs.2011.05.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009481659
306 rdf:type schema:CreativeWork
307 https://doi.org/10.1016/j.pharmthera.2012.12.007 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026929795
308 rdf:type schema:CreativeWork
309 https://doi.org/10.1016/j.toxlet.2010.06.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045245431
310 rdf:type schema:CreativeWork
311 https://doi.org/10.1046/j.1365-2362.2003.01154.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1024326295
312 rdf:type schema:CreativeWork
313 https://doi.org/10.1053/jhep.2002.33215 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037448276
314 rdf:type schema:CreativeWork
315 https://doi.org/10.1096/fj.02-0195fje schema:sameAs https://app.dimensions.ai/details/publication/pub.1027353228
316 rdf:type schema:CreativeWork
317 https://doi.org/10.1097/00000542-198407000-00006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009301650
318 rdf:type schema:CreativeWork
319 https://doi.org/10.1097/00008571-200004000-00001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1060289721
320 rdf:type schema:CreativeWork
321 https://doi.org/10.1097/pcc.0b013e3181fe406d schema:sameAs https://app.dimensions.ai/details/publication/pub.1060343647
322 rdf:type schema:CreativeWork
323 https://doi.org/10.1111/dme.12360 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004301534
324 rdf:type schema:CreativeWork
325 https://doi.org/10.1111/j.1365-2044.1987.tb03086.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1048949424
326 rdf:type schema:CreativeWork
327 https://doi.org/10.1111/j.1365-2125.2005.02389.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1019539043
328 rdf:type schema:CreativeWork
329 https://doi.org/10.1124/dmd.109.027466 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033292654
330 rdf:type schema:CreativeWork
331 https://doi.org/10.1146/annurev.pharmtox.46.120604.141059 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014053236
332 rdf:type schema:CreativeWork
333 https://doi.org/10.1158/1078-0432.ccr-06-0023 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010686656
334 rdf:type schema:CreativeWork
335 https://doi.org/10.1159/000318741 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044091234
336 rdf:type schema:CreativeWork
337 https://doi.org/10.1172/jci200525102 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063416820
338 rdf:type schema:CreativeWork
339 https://doi.org/10.1172/jci25102 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004145275
340 rdf:type schema:CreativeWork
341 https://doi.org/10.2174/1389200043335559 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069175464
342 rdf:type schema:CreativeWork
343 https://doi.org/10.2174/138920007782109733 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069175656
344 rdf:type schema:CreativeWork
345 https://www.grid.ac/institutes/grid.415960.f schema:alternateName St. Antonius Ziekenhuis
346 schema:name Department of Anaesthesiology, Intensive Care and Pain Management, St. Antonius Hospital, Nieuwegein, The Netherlands
347 Department of Clinical Pharmacy, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands
348 Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
349 Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
350 rdf:type schema:Organization
351 https://www.grid.ac/institutes/grid.418011.d schema:alternateName Centre for Human Drug Research
352 schema:name Centre for Human Drug Research (CHDR), Leiden, The Netherlands
353 Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
354 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...