Pharmacokinetics of pentopril in the elderly.
1 The pharmacokinetics of pentopril in elderly subjects aged 70 to 75 years were compared with those of healthy young subjects aged 22 to 26 years. 2 There were no appreciable differences between the two groups in any of the pharmacokinetic parameters for pentopril derived from its plasma data (Cmax, tmax, AUC and t1/2). 3 In contrast, the active metabolite CGS 13934 exhibited an increase in mean values of AUC by 56% in elderly compared to young. However, the difference was not statistically significant (0.1 greater than P greater than 0.05). The variability was, however, significantly higher (P less than 0.05) in the elderly group compared with young. The peak time for metabolite was also significantly delayed in elderly (3.9 vs 2.5 h). The mean half-life for metabolite however, was comparable for the two groups (3.6 vs 3.9 h). 4 Urinary analysis showed a significant decrease in renal clearance (CLR) with age for both pentopril (107 vs 203 ml min-1) and its active metabolite (116 vs 205 ml min-1). 5 Pharmacodynamic measurements of the renin-angiotensin system, in general, demonstrated a drug effect at 2 h with recovery almost to the basal value at 24 h except for plasma ACE activity at 24 h in the elderly. 6 Because of large variability and an increase in the mean AUC of active metabolite in elderly, greater caution may be necessary for dose selection in this group. However, no substantial difference in extent of drug accumulation is anticipated in elderly compared with young people based on the similarity in t1/2 values.
Rakhit
A
A
Pharmaceuticals Division CIBA-GEIGY Corporation, Ardsley, NY.
Kochak
G M
GM
Tipnis
V
V
Radensky
P
P
Hurley
M E
ME
Williams
R
R
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D000450:Aldosterone; C038810:CGS 13945; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A