Effect of hydrochlorothiazide on the pharmacokinetics of enalapril in hypertensive patients with varying renal function.
An open, randomised, cross-over study was performed to investigate the pharmacokinetics of enalaprilat, administered as 20 mg enalapril both as monotherapy and in combination with hydrochlorothiazide (HCTZ 12.5 mg). Three groups of 6 hypertensive patients were enrolled [untreated diastolic blood pressure (DBP) 90-115 mm Hg]; normal renal function [glomerular filtration rate (GFR) > 81 ml min-1 1.73 m-2], mild renal impairment (GFR 51-80 ml min-1 1.73 m-2), and moderate renal impairment (GFR 31-50 ml min-1 1.73 m-2). The pharmacokinetics of enalaprilat and enalaprilat plus HCTZ correlated predictably with renal impairment with increased plasma concentrations and decreased urinary elimination at lower values of GFR. The coadministration of HCTZ had no significant effect on the pharmacokinetics of enalaprilat in any group. We conclude that although the pharmacokinetics of both enalaprilat and HCTZ are related to renal function, HCTZ has no significant effect on the pharmacokinetics of enalaprilat and that dosage adjustment for both regimens should be based on renal function.
Hersh
A D
AD
Merck Sharp & Dohme Limited, Hoddesdon, Herts, Dublin, Ireland.
Kelly
J G
JG
Laher
M S
MS
Carmody
M
M
Doyle
G D
GD
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D004232:Diuretics; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D049993:Sodium Chloride Symporter Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D004656:Enalapril