ABSENCE OF A PHARMACOKINETIC INTERACTION BETWEEN LOSARTAN AND HYDROCHLOROTHIAZIDE

To support the use of a combination of losartan, a highly specific and selective AT, angiotensin II receptor antagonist, and hydrochlorothia zide for treatment of hypertension, a pharmacokinetic drug interaction study was conducted, In this open-label, randomized, three-period, cr ossover study, patients with mild to moderate hypertension received a 12.5-mg tablet of hydrochlorothiazide, a 50-mg losartan tablet, or a c ombination tablet of 12.5 mg of hydrochlorothiazide and 50 mg of losar tan for 7 days. Twelve patients (age range, 35-55 years; mean age, 44 years) were allocated to treatment. Drug interactions were Evaluated b y comparing the 24-hour area under the concentration-time curve (AUC(2 4)) for losartan and its active metabolite, E-3174, when losartan (50 mg) was given alone or in combination with 12.5 mg hydrochlorothiazide . The urinary recovery over the 24-hour period of hydrochlorothiazide was compared for hydrochlorothiazide (12.5 mg) given alone or in combi nation with 50 mg losartan. A clinically significant interaction was d efined as a treatment difference of more than 35%. There was no eviden ce of a clinically significant effect of hydrochlorothiazide on the ph armacokinetics of losartan or E-3174, as the geometric mean AUC(24) ra tio (90% confidence interval [CI]) was 1.02 (0.95, 1.09) for losartan and 1.02 (0.96, 1.09) for E-3174. Based on urinary recovery over a 24- hour period of hydrochlorothiazide, losartan did not affect the pharma cokinetics of hydrochlorothiazide, as the geometric mean ratio of urin ary hydrochlorothiazide recovery (90% CI) was 0.898 (0.79, 1.20). Ther e was a minor (17%) decrease in the AUC(24) of hydrochlorothiazide aft er administration of the combination tablet. Coadministration of hydro chlorothiazide and losartan was well tolerated.