In a randomized, cross-over, single-dose study of 19 elderly hypertensive patients (aged 62–84 y, SBP > 160 mm Hg, DBP > 100 mm Hg, creatinine clearance 11–93 ml·min−1) we have studied the pharmacokinetics of the angiotensin converting enzyme (ACE) inhibitor enalapril after a single oral dose of either 10 mg enalapril or 10 mg enalapril + 25 mg hydrochlorothiazide.
The pharmacokinetics of enalapril were unaffected by hydrochlorothiazide, but there was a significant reduction in renal clearance and a significant increase in AUC(0–24 h) of enalaprilat after hydrochlorothiazide, resulting in higher serum concentrations of the active drug. This was independent of the individual degree of renal impairment and might be due either to an initial reduction of GFR by hydrochlorothiazide or to interference with the tubular secretion of enalaprilat.
The relationships between serum enalaprilat and serum ACE activity were similar after both treatments, both consistent with a value for Ki of enalaprilat of about 0.1 nmol·l−1. Thus, serum ACE activity was not affected by hydrochlorothiazide but completely reflected the pharmacokinetics of enalaprilat in both treatments.
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Weisser, K., Schloos, J., Jakob, S. et al. The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients. Eur J Clin Pharmacol 43, 173–177 (1992). https://doi.org/10.1007/BF01740666
- renal impairment
- old patients