Effect of CYP3A5 and ABCB1 polymorphisms on the interaction between tacrolimus and itraconazole in patients with connective tissue disease View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2015-07-17

AUTHORS

Masaru Togashi, Takenori Niioka, Atsushi Komatsuda, Mizuho Nara, Shin Okuyama, Ayumi Omokawa, Maiko Abumiya, Hideki Wakui, Naoto Takahashi, Masatomo Miura

ABSTRACT

PurposeThe aim of this study was to investigate the effect of itraconazole (ITCZ), a potent inhibitor of CYP3A4 and P-glycoprotein, on the blood concentration 12 h after tacrolimus administration (C12h) in relation to CYP3A5 6986A>G and ABCB1 3435C>T genotype status in patients with connective tissue disease (CTD).MethodsEighty-one CTD patients taking tacrolimus (Prograf®) once daily at night (2100 hours) were enrolled in this study. Whole blood samples were collected 12 h after tacrolimus administration at steady state.ResultsThe dose-adjusted tacrolimus C12h with or without ITCZ co-administration was significantly higher in patients with CYP3A5*3/*3 than in those with the CYP3A5*1 allele [CYP3A5 *1/*1 vs. *1/*3 vs. *3/*3 = 1.67 vs. 2.70 vs. 4.83 ng/mL/mg (P = 0.003) and 0.68 vs. 0.97 vs. 2.20 ng/mL/mg (P < 0.001), respectively], but differences were not observed for ABCB1 genotypes. However, there was no difference in the increase rate of the dose-adjusted C12h of tacrolimus between CYP3A5 or ABCB1 genotypes (P = 0.378 and 0.259). On the other hand, reduction of the estimated glomerular filtration rate exhibited a correlation with the C12h of tacrolimus after ITCZ co-administration (r = −0.482, P = 0.009).ConclusionsIn CYP3A5*3/*3 patients, because the metabolic pathway for tacrolimus occurs only through CYP3A4, the combination with ITCZ seems to lead to a higher risk of acute renal dysfunction. Therefore, we suggest that the target blood tacrolimus concentration be set as low as possible through dose-adjustment for patients with the CYP3A5*3/*3 allele. More... »

PAGES

1091-1097

References to SciGraph publications

  • 2011-12. Triazole Antifungal Agents in Invasive Fungal Infections in DRUGS
  • 2013-01-26. Effect of itraconazole on the concentrations of tacrolimus and cyclosporine in the blood of patients receiving allogeneic hematopoietic stem cell transplants in EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
  • 2003-06. Tacrolimus in DRUGS
  • 2003-09-17. The effect of age, sex, and rifampin administration on intestinal and hepatic cytochrome P450 3A activity in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2015-02-12. The donor ABCB1 (MDR-1) C3435T polymorphism is a determinant of the graft glomerular filtration rate among tacrolimus treated kidney transplanted patients in JOURNAL OF HUMAN GENETICS
  • 2009-11. Antifungal Prophylaxis and Pre-Emptive Therapy in DRUGS
  • 2010-04. Effect of CYP3A and ABCB1 Single Nucleotide Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Calcineurin Inhibitors: Part II in CLINICAL PHARMACOKINETICS
  • 2002-09. Mechanisms of Clinically Relevant Drug Interactions Associated with Tacrolimus in CLINICAL PHARMACOKINETICS
  • 2001-12. Clinical Experience with Itraconazole in Systemic Fungal Infections in DRUGS
  • 2010-08-25. Accurate Prediction of Dose‐Dependent CYP3A4 Inhibition by Itraconazole and Its Metabolites From In Vitro Inhibition Data in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2010-12-29. Efficacy and safety of tacrolimus for induction therapy in patients with active lupus nephritis in MODERN RHEUMATOLOGY
  • 2010-03. Effect of CYP3A and ABCB1 Single Nucleotide Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Calcineurin Inhibitors: Part I in CLINICAL PHARMACOKINETICS
  • 2004-08. Clinical Pharmacokinetics and Pharmacodynamics of Tacrolimus in Solid Organ Transplantation in CLINICAL PHARMACOKINETICS
  • 2013-11-19. The Role of Pharmacogenetics in the Disposition of and Response to Tacrolimus in Solid Organ Transplantation in CLINICAL PHARMACOKINETICS
  • 2005-08-11. Effect of itraconazole on the pharmacokinetics and pharmacodynamics of fexofenadine in relation to the MDR1 genetic polymorphism in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 2001-03-18. Frequency of single nucleotide polymorphisms in the P‐glycoprotein drug transporter MDR1 gene in white subjects in CLINICAL PHARMACOLOGY & THERAPEUTICS
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    http://scigraph.springernature.com/pub.10.1007/s00228-015-1901-4

    DOI

    http://dx.doi.org/10.1007/s00228-015-1901-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1015534333

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26184414


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