The pharmacokinetics of angiotension converting enzyme (ACE) inhibitors enalapril (10 mg orally) and its active metabolite, enalaprilat (10 mg intravenously) were studied in nine young healthy volunteers aged 22‐30 years and nine sex matched elderly subjects aged 65‐73 years. After both drugs, a biexponential curve was fitted to the decline in plasma enalaprilat concentration. Area under the plasma concentration‐time curve (AUC) was greater in the elderly for both drugs. Clearance (CL) and clearance/bioavailability (CL/F) were less in the elderly for enalaprilat and enalapril, respectively. There was no difference in F between young (0.62 +/‐ 0.16) and elderly subjects (0.61 +/‐ 0.15). Enalaprilat CL and enalapril CL/F were significantly and positively correlated to endogenous creatinine clearance. There was a significant difference in the weight corrected volume of distribution at steady state after enalaprilat between the young and elderly (P less than 0.02). The relationship between plasma enalaprilat concentrations and percentage ACE inhibition, using the Hill equation, showed no difference in the sensitivity to ACE inhibition between the young and the elderly group. The pharmacokinetic differences observed are likely to be related to an age dependent decline in renal function as well as changes in body composition. Kinetic differences partly explain the greater pharmacodynamic response in the elderly.

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1 The effect of cimetidine on oxidative drug metabolism was characterised using antipyrine clearance in a group of healthy volunteers. 2 In six subjects cimetidine produced a dose dependent reduction of antipyrine clearance: 400 mg/day (16.8 + 2.2%, mean + s.e. mean), 800 mg/day (26.3 + 1.5%) and 1600 mg/day (33.5 + 2.4%). 3 The effect of cimetidine (800 mg/day) was of similar magnitude (approximately 25%) in two groups of six young (21-26 years) and six elderly (65-78 years) subjects.4 The effect of pretreatment begun just 1 h before administration of antipyrine was similar to that of 24 h pretreatment and that reported for chronic cimetidine pretreatment. 5 The percentage reduction in antipyrine clearance produced by cimetidine 800 mg/day was greater (44 + 5 vs 24 + 3%; P < 0.05) in six subjects who had been pretreated with the hepatic enzyme inducer rifampicin (600 mg/day for 21 days) than in the control uninduced state.6 Although cimetidine was capable of rapidly reversing the effect of rifampicin on antipyrine clearance, following withdrawal of both rifampicin and cimetidine there was still evidence of enzyme induction. 7 These results suggest that the effect of cimetidine on oxidative metabolism is dose dependent, is more marked in enzyme induced subjects, is independent of the duration of pretreatment and is of similar magnitude in young and elderly subjects.

The pharmacokinetics and effect of single oral doses of carbamazepine (400 mg) were compared in a group of six young volunteers aged between 20 and 25 years, and a second group of five elderly volunteers aged between 66 and 84 years. No age related changes in salivary or plasma pharmacokinetics or in psychomotor function were detected.