Author/Editor		Herman, Darja; Locatelli, Igor; Grabnar, Iztok; Peternel, Polona; Stegnar, Mojca; Lainščak, Mitja; Mrhar, Aleš; Breskvar, Katja; Dolžan, Vita
Title		The influence of co-treatment with carbamazepine, amiodarone and statins on warfarin metabolism and maintance dose
Type		članek
Source		Eur J Pharmacol
Vol. and No.		Letnik 62, št. 4
Publication year		2006
Volume		str. 291-6
Language		eng
Abstract		Aims: Warfarin is a frequently used anticoagulant during with natrow therapeutic index and high interindividual variability in the dose requirement. We have previously shown that warfarin dose is influenced by cytochrome P450 (CYP) 2C9 genotype, age, body weight and co-treatment with drugs that interfere with warfarin metabolism. As, in many patients, drug co-treatment cannot be avoided, we investigated the effect of co-treatment with carbamazepine, amiodarone and statins on warfarin metabolism and maintenance dose. Methods: Caucasian patients on stable maintenance warfarin therapy with CYP2C9* 1 /*1 genotype (n=82) were included in the study. Plasma concentradons of (S)- and (R)-warfarin as well as warfarin hydroxylated metabolites were determined using HPLC assay and cornesponding clearances of (S)- and (R)-warfarin were calculated. Results: Patients co-treated with carbamazepine (n=5) had significantly higher plasma 10-hydroxywarfarin concentrations than patients not taking any interacting drugs (n=54) (median: 0.327 mig/ml vs 0.030 mig/ml, p=0.003). (S)- and (R)-warfarin clearances were also higher in the carbamazepine co-treated group (p=0.003), as were warfarin dose requirements (median: 9.00 mg/day vs 3.86 mg/day, p=0.003). Under the conditions of this study, patients co-treated with amiodarone (n=6) did not differ significantly regarding any measured characteristic from patients with no interacting drug treatment, while patients co-treated with simvastatin or lovastatin (n=17) had Lower 10-hydroxywarfarin concentration (p=0.02). Conclusions: We confirmed important interaction between carbamazepine and warfarin metabolism which can be of major clinical importance. If treatment wit6 carbamazepine cannot be avoided, patients taking warfarin should be frequently monitored, especially when initiating or stopping carbamazepine therapy.
Descriptors		DRUG THERAPY, COMBINATION CARBAMAZEPINE AMIODARONE HYDROXYMETHYLGLUTARYL COA REDUCTASES WARFARIN DRUG INTERACTIONS GENOTYPE CYTOCHROME P-450 CHROMATOGRAPHY, HIGH PRESSURE LIQUID