Aspects on pharmacokinetics of some diuretics

Abstract

This review summarizes the present knowledge of some commonly used diuretics. Bendroflumethiazide and bumetanide are completely absorbed from the gut while the uptake of hydrochlorothiazide, chlorthalidone and furosemide averages about 65%. The degree of uptake of amiloride and spironolactone is unknown but exceeds 50%. Plasma t 1/2 of bumetanide and furosemide are approximately 1 h. The clinically important phase of the plasma concentration of bendroflumethiazide has a t 1/2 of 3 h, although a slower phase with a t 1/2 of 9 h has been described. Hydrochlorothiazide and amiloride, often used in combination, both have a t 1/2 of about 10 h. Canrenone, an active metabolite of spironolactone, has a t 1/2 of 15-20 h. Chlorthalidone is eliminated very slowly with a t 1/2 of about two days. This is partly caused by an extensive binding to carbonic anhydrase in the erythrocytes. The protein binding of bendroflumethiazide, bumetanide, canrenone and furosemide is approximately 95%. The binding of chlorthalidone and hydrochlorothiazide is about 75 and 40% respectively. All mentioned diuretics except spironolactone are in part eliminated renally, mainly via tubular secretion. This is the major elimination route for amiloride and hydrochlorothiazide, while it constitutes one third to two thirds for bendroflumethiazide, bumetanide and furosemide. Spironolactone is exclusively eliminated as metabolites.