Population Pharmacokinetic and Dynamic Analysis of the Topoisomerase I Inhibitor Lurtotecan in Phase II Studies View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-02

AUTHORS

J.H.M. Schellens, B. Heinrich, M. Lehnert, M.E. Gore, S.B. Kaye, P. Dombernowsky, R. Paridaens, A.T. van Oosterom, J. Verweij, W.J. Loos, H. Calvert, N. Pavlidis, H. Cortes-Funes, J. Wanders, M. Roelvink, C. Sessa, K. Selinger, P.S. Wissel, T. Gamucci, A.R. Hanauske

ABSTRACT

Population pharmacokinetic-dynamic analysis was prospectively integrated in a broad phase II program of lurtotecan (GI147211), a novel camptothecin derived topoisomerase I inhibitor, to determine the population pharmacokinetic profile in a larger population, to estimate individual pharmacokinetic parameters and to investigate relationships with clinical outcome. A sparse sampling method was applied during course one, which involved two sampling time-points. A Bayesian algorithm was used to estimate individual pharmacokinetic parameters, in particular total plasma clearance (CL) and volume of distribution. In total, samples were collected of 109 (63%) of 173 patients. Pharmacokinetic-dynamic evaluation could be carried out successfully in 85 (78%) of the sampled patients. CL of lurtotecan showed substantial variability (mean 87 +/- 28 L/h) and was of the same magnitude as in the phase I studies where full pharmacokinetic curves were used. Residual variability in the population estimate of CL was 9.9%. No significant relationships were observed between exposure parameters and toxicity nor likelihood of tumor response, however the latter relationship may well have been obscured by the heterogeneity of the studied population. Prospective implementation of large scale population pharmacokinetic-dynamic analysis is feasible and important to establish whether interpatient variability in drug exposure is a major determinant of toxicity or activity. More... »

PAGES

83-93

References to SciGraph publications

  • 1996-06. Docetaxel serum protein binding with high affinity to alpha1-acid glycoprotein in INVESTIGATIONAL NEW DRUGS
  • 1991-06. Designs for population pharmacodynamics: Value of pharmacokinetic data and population analysis in JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
  • 1995-05. Pharmacokinetics and pharmacodynamics of topotecan administered daily for 5 days every 3 weeks in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 1981-12. Understanding the Dose-Effect Relationship in CLINICAL PHARMACOKINETICS
  • 1995-01. Population pharmacokinetics of docetaxel during phase I studies using nonlinear mixed-effect modeling and nonparametric maximum-likelihood estimation in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 1996-03. Phase I and pharmacological study of the new topoisomerase I inhibitor GI147211, using a daily x 5 intravenous administration in BRITISH JOURNAL OF CANCER
  • 1996-01. Emerging Drug Treatments for Solid Tumours in DRUGS
  • 1996-02. The Use of Population Pharmacokinetics in Drug Development in CLINICAL PHARMACOKINETICS
  • 1997-10. The bioavailability of oral GI147211 (GG211), a new topoisomerase I inhibitor in BRITISH JOURNAL OF CANCER
  • 1992-04. Opportunities for integration of pharmacokinetics, pharmacodynamics, and toxicokinetics in rational drug development in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 1985-11. Premarketing observational studies of population pharmacokinetics of new drugs in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 1981-08. Some suggestions for measuring predictive performance in JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1023/a:1014454821885

    DOI

    http://dx.doi.org/10.1023/a:1014454821885

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1013802648

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/12003197


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