Screening for the influence of host factors on warfarin clearance using a single dose single sample procedure.
A single dose, single sample procedure for estimating warfarin clearance for screening purposes was evaluated. Single sample estimates of warfarin clearance, CL/F, were closest to actual values for warfarin clearance, CL/F, calculated from multiple sample data when the sample was collected 120 h after warfarin ingestion. An apparent volume of distribution, V/F, of 0.17 l/kg was used in calculating CL/F. After a single dose of warfarin single sample values of CL/F averaged 0.243 l/h +/- 0.042 (N = 12) which compared well with a multiple sample-based value of CL/F which was 0.243 l/h +/- 0.046 (N = 12). When an erythromycin pretreatment was started before warfarin ingestion and continued throughout the period of warfarin elimination CL/F decreased to 0.208 l/h +/- 0.047 while CL/F decreased to 0.210 l/h +/- 0.061. Mean prediction error for CL/F relative to CL/F was -0.001 l/h with a 95% confidence interval of -0.010 to 0.009 l/h. Warfarin is a drug with pharmacokinetic characteristics enabling it to be used in a single dose single sample procedure in screening for host factor influences on its clearance.
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Bachmann
D000328:Adult; D004347:Drug Interactions; D004917:Erythromycin / Q000008:administration & dosage; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism
D014859:Warfarin; D004917:Erythromycin