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Amiodarone decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Warfarin excretion products were quantified and clearance and formation clearance values calculated. Amiodarone and metabolites inhibited the reduction of (R)-warfarin to (R,S)-warfarin alcohol-1 and the oxidation of(More)
To evaluate a stereoselective interaction for amiodarone and racemic warfarin, we performed a prospective study with its separated enantiomorphs. Single oral doses of racemic warfarin, 1.5 mg/kg, were administered to six normal subjects, with and without oral amiodarone, 400 mg daily, for the hypoprothrombinemic duration. Both the hypoprothrombinemia (P(More)
Samples of urine and feces were collected daily from a normal human volunteer who had received a dose of pseudoracemic phenprocoumon [an equimolar mixture of (R)-[12C]- and (S)-[2-13C]phenprocoumon] containing a tracer dose of 10 microCi of [14C]phenprocoumon and analyzed by TLC, HPLC, and GC-MS. After 25 days, 96% of the radiolabeled material was recovered(More)
Miconazole decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Miconazole inhibited the oxidation of both (R)- and (S)-warfarin to phenolic metabolites, although (S)-warfarin was inhibited to the greater extent. In particular, (S)-7-hydroxylation, the pathway primarily responsible(More)
To better understand how smallholder farmers whom own the majority of Cambodian cattle can contribute to efforts to address food security needs in the Mekong region, a five-year research project investigating methods to improve cattle health and husbandry practices was conducted. Cattle production in Cambodia is constrained by transboundary animal diseases(More)
The goal of the study was to test the assumption that a competitive inhibition constant determined in vivo, Kiiv, like its corresponding in vitro counterpart, Ki, is independent of inhibitor concentration. Inhibition of the CYP2C9-dependent formation of (S)-7-hydroxy-warfarin from (S)-warfarin was measured in seven healthy subjects at three different doses(More)
To allow the simultaneous evaluation of the interaction between sulfinpyrazone and each enantiomer of racemic warfarin, pseudoracemic warfarin (1:1 12C-R(+) and 13C-S(-)warfarin) was given to six normal subjects both before and during oral sulfinpyrazone dosing. Serial blood and urine samples were analyzed for unchanged warfarin and its metabolic products(More)
Spironolactone has been reported to diminish the hypoprothrombinemic effect of oral anticoagulants in animals and digitoxin blood levels in man by induction of hepatic enzymes. To evaluate this in man, single oral doses of racemic warfarin, 1.5 mg/kg body weight, with and without 200 mg oral spironolactine daily, were administered to 9 normal subjects.(More)
Cimetidine potentiates the anticoagulant effect of warfarin sodium, but in one small study ranitidine hydrochloride did not. Furthermore, these drugs have not been compared in the same subjects. Eleven normal subjects received single oral doses of 1.5 mg/kg racemic warfarin sodium alone, with cimetidine (1,200 mg/day orally), or with ranitidine (300 mg/day(More)