A comparison of the relative sensitivities of factor VII and prothrombin time measurements in detecting drug interactions with warfarin.
We have studied the comparative abilities of the prothrombin time and factor VII clotting activity, measured using a chromogenic assay, to detect drug interactions with warfarin. Pharmacokinetic and pharmacodynamic data were collected from studies involving the single administration of 25 mg of warfarin in the absence and presence of fengabin, cimetidine, ranitidine, and enoxacin. Fengabin caused changes in both the pharmacokinetics and pharmacodynamics of warfarin, whereas cimetidine and enoxacin only caused changes in its pharmacokinetics. Ranitidine had no effect on either the pharmacokinetics or pharmacodynamics of warfarin. In general, factor VII clotting activity showed greater sensitivity but also greater variability than the prothrombin time to changes in clotting activity. Consequently, factor VII clotting activity did not have greater discriminatory power than the prothrombin time in detecting drug interactions involving warfarin.
Pitsiu
M
M
Department of Pharmacy, University of Manchester, UK.
Parker
E M
EM
Aarons
L
L
Holt
B
B
Rowland
M
M
D000328:Adult; D002733:Chlorophenols / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D015365:Enoxacin / Q000494:pharmacology; D005167:Factor VII / Q000187:drug effects*; D006801:Humans; D008297:Male; D011517:Prothrombin Time; D011899:Ranitidine / Q000494:pharmacology; D013237:Stereoisomerism; D014859:Warfarin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014914:Whole Blood Coagulation Time
D002733:Chlorophenols; D015365:Enoxacin; D014859:Warfarin; D002927:Cimetidine; D011899:Ranitidine; D005167:Factor VII; C052028:fengabine