1 The pharmacokinetics of enalaprilat were studied after administration of single and multiple doses of enalapril maleate to people with normal and impaired renal function. 2 Renal impairment was associated with higher serum concentrations of enalaprilat, longer times to peak concentrations, slower decline of serum concentrations and with reduced urinary elimination. Urinary elimination of enalaprilat was closely related to renal function.3 In patients with severe renal impairment (GFR values below 30 ml min7l 1.73 m-2) significantly smaller doses of enalapril maleate will be required than in patients with normal or less severely impaired renal function.

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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.