Population pharmacokinetics of racemic warfarin in adult patients

D. R. Mungall, T. M. Ludden, J. Marshall, D. W. Hawkins, R. L. Talbert, M. H. Crawford

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

The population pharmacokinetics of racemic warfarin was evaluated using 613 measured warfarin plasma concentrations from 32 adult hospitalized patients and 131 adult outpatients. Warfarin concentrations were measured in duplicate using a high-performance liquid chromatographic procedure. The pharmacokinetic model used was a one-compartment open model with first-order absorption (absorption rate constant set equal to 47 day-1) and first-order elimination. The extent of availability was assumed to be one. A linear regression model was used to evaluate the influence of various demographic factors on warfarin oral clearance. Age appeared to be an important determinant of warfarin clearance in this adult population. There was about a 1%/year decrease in oral clearance over the age range of 20-70 years. Smoking appeared to result in a 10% increase in warfarin clearance, while coadministration of the inducers phenytoin or phenobarbital yielded about a 30% increase in clearance. This study has yielded a predictive model that, when combined with appropriate pharmacological response data, may be useful in the design and adjustment of warfarin regimens.

Original languageEnglish (US)
Pages (from-to)213-227
Number of pages15
JournalJournal of Pharmacokinetics and Biopharmaceutics
Volume13
Issue number3
DOIs
StatePublished - Jun 1 1985

Keywords

  • age and kinetics
  • anticoagulants
  • population analysis
  • warfarin kinetics

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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