Pharmacodynamics of uniform versus nonuniform warfarin dosages.
OBJECTIVE
To compare the pharmacodynamics of uniform versus nonuniform warfarin dosages.


METHODS
Prospective, randomized, crossover study.


METHODS
Anticoagulation clinic.


METHODS
Twenty healthy subjects who had the extensive metabolizer cytochrome P450 (CYP) genotype of 2C9*1/*1 or CYP2C9*1/*3.


METHODS
Subjects received either warfarin 5.75 mg once/day (two 1-mg tablets plus one and a half 2.5-mg tablets) as part of the uniform dosage group or warfarin 7.5 mg/day on Mondays and Fridays and 5 mg/day on each of the remaining days of the week as part of the nonuniform dosage group. Subjects received the first regimen for 17 days, had a 2-week washout period, and then were switched to the other regimen for another 17 days.


RESULTS
During both treatment periods, international normalized ratios (INRs) were checked daily using a fingerstick method. Any changes in concomitant drug therapy, including over-the-counter and supplement products, as well as health status were recorded. The Scheffe post hoc test revealed no significant differences in mean INR values obtained during receipt of the two dosage regimens. In both dosage groups, variation in the INR became more pronounced as INR values increased. No adverse events (i.e., major or minor bleeding) or changes in drug therapy were reported during the study.


CONCLUSIONS
Our findings suggest that it is safe to use a nonuniform dosage regimen of warfarin to reach a target INR range. With both uniform and nonuniform regimens, close monitoring remains important to ensure that patients remain within the desired INR range.
Hameed
Mohamed S
MS
Eastern Maine Inpatient Care, Eastern Maine Medical Center, Bangor, Maine, USA.
Nafziger
Anne N
AN
Gartung
Anne M
AM
Bertino
Joseph S
JS
D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011446:Prospective Studies; D014859:Warfarin / Q000008:administration & dosage* / Q000494:pharmacology
D000925:Anticoagulants; D014859:Warfarin