PHARMACOKINETIC DRUG-INTERACTION STUDIES WITH CANDESARTAN CILEXETIL

The aim of this series of studies was to determine the potential for p harmacokinetic interaction between candesartan (administered orally as the prodrug candesartan cilexetil) and hydrochlorothiazide (HCTZ), ni fedipine, glibenclamide, warfarin, digoxin or the components of an ora l contraceptive formulation. All studies were performed in healthy vol unteers using randomised, crossover or add-on study designs. Candesart an cilexetil was administered orally at doses of 8, 12 or 16 mg. The p harmacokinetic parameters were determined for comparator agents and ca ndesartan following administration of each agent alone or in combinati on. There were no changes in the drug plasma concentrations of nifedip ine, glibenclamide, digoxin or oral contraceptives when co-administere d with candesartan cilexetil. Co-administration of candesartan cilexet il caused a slight but significant decrease in the AUC of HCTZ. Howeve r, the 90% confidence intervals (CI) for AUC ratios for HCTZ when co-a dministered with candesartan cilexetil were within the defined limits of bioequivalence. Candesartan cilexetil produced a 7% decrease in tro ugh plasma warfarin concentration but this had no effect on prothrombi n time. Co-administration of candesartan cilexetil with HCTZ produced a statistically significant increase in the bioavailability and C-max values for candesartan (18% and 25%, respectively). However, this incr ease is not considered to be clinically relevant. No other co-administ ered drug (nifedipine, glibenclamide, digoxin, oral contraceptive) aff ected the pharmacokinetic parameters of candesartan. Candesartan cilex etil was well tolerated both alone and in combination with the other a gents.