Lack of pharmacokinetic and pharmacodynamic interactions between a smoking cessation therapy, varenicline, and warfarin: an in vivo and in vitro study.
J Clin Pharmacol
; 47(11): 1421-9, 2007 Nov.
Article
en En
| MEDLINE
| ID: mdl-17962429
ABSTRACT
This study investigated the effect of varenicline on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in 24 adult smokers and compared these findings with data generated using human in vitro systems. Subjects were randomized to receive varenicline 1 mg twice a day or placebo for 13 days and then switched to the alternative treatment after a 1-week washout period. A single dose of warfarin 25 mg was given on day 8 of each treatment period, and serial blood samples were collected over 144 hours postdose. Pharmacokinetic parameters for both (R)- and (S)-warfarin and international normalized ratio (INR) values were determined. Varenicline was assessed as an inhibitor and inducer of human cytochrome P450 activities using liver microsomes and hepatocytes, respectively. Consistent with the in vitro data, no alteration in human pharmacokinetics of warfarin enantiomers was observed with varenicline treatment. The 90% confidence intervals for the ratios of area under the concentration-time curve from zero hours to infinity and peak plasma concentrations were completely contained within 80% to 125%. Warfarin pharmacodynamic parameters, maximum INR, and the area under the prothrombin (INR)-time curve, were also unaffected by steady-state varenicline. Concomitant administration of varenicline and warfarin was well tolerated. Consequently, warfarin can be safely administered with varenicline without the need for dose adjustment.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quinoxalinas
/
Warfarina
/
Benzazepinas
/
Cese del Hábito de Fumar
/
Anticoagulantes
Tipo de estudio:
Clinical_trials
Límite:
Adolescent
/
Adult
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Clin Pharmacol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos