Pharmacokinetic interaction study with fixed high dose combinations of candesartan cilexetil and hydrochlorothiazide

Combination treatment with candesartan and hydrochlorothiazide (HCT) has been shown to provide the full additive antihypertensive effect of the components. A clinical program has been undertaken to study the efficacy and safety of the fixed dose combinations of candesartan 32 mg and HCT 12.5 or 25 mg in patients with mild to moderate hypertension. This study evaluated the drug-drug interaction potential of the highest dose combination of candesartan 32 mg and HCT 25 mg.

53 healthy male and female subjects were randomized to sequential treatment with single doses of one candesartan/ HCT 32/25 mg tablet, two 16/12.5 mg tablets, one candesartan 32 mg tablet and one HCT 25 mg tablet using an open 4-way cross-over design.

There was no pharmacokinetic interaction between candesartan 32 mg and HCT 25 mg during concomitant administration. AUC and Cmax were within the accepted confidence limits of 0.8 - 1.25 compared to the monocomponents, and tmax and t1/2 were similar to those of the monocomponents. There were no unexpected safety findings, and no subject discontinued study treatment due to an adverse event.

There was no pharmacokinetic interaction found between the high doses of candesartan 32 mg and HCT 25 mg.