A pharmacokinetic study of cilazapril in elderly and young volunteers.
1. Cilazaprilat is an inhibitor of angiotensin converting enzyme (ACE) and is the active metabolite of cilazapril. The pharmacokinetics of cilazaprilat, and the inhibition of plasma ACE were investigated in 12 elderly and 12 young healthy volunteers. 2. Single oral 1 mg doses of cilazapril were given to the elderly (age range 65-83 years) and the young (age range 18-31 years) in an open study. Plasma and urinary cilazaprilat concentrations, and plasma ACE activities were measured up to 72 h after dosing by radioenzymatic methods. 3. Cilazapril was well tolerated in both young and elderly subjects. Small falls in blood pressure were observed up to 8-24 h after dosing. 4. The mean peak plasma cilazaprilat concentration in the elderly (11.5 ng ml-1) was significantly greater (P less than 0.02) than the corresponding value in the young (8.3 ng ml-1). Total and renal clearances were significantly lower (both P less than 0.05) in the elderly (12.8 and 5.11 h-1) than in the young (16.0 and 7.21 h-1). Total urinary recovery of cilazaprilat was similar for the two groups at about 43% of dose. 5. Plasma ACE inhibition was slightly greater in the elderly but the mean inhibition in the two groups did not differ by more than 10% at any time-point from 1-72 h. 6. The plasma concentrations of cilazaprilat required for 90% ACE inhibition were similar at 4.7 and 4.8 ng ml-1 in the elderly and young respectively. 7. It is concluded that the age-related changes in cilazaprilat kinetics and in the degree of ACE inhibition are small.(ABSTRACT TRUNCATED AT 250 WORDS)
Williams
P E
PE
Roche Products Ltd, Welwyn Garden City, Herts.
Brown
A N
AN
Rajaguru
S
S
Walters
G E
GE
McEwen
J
J
Durnin
C
C
D000284:Administration, Oral; D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D001835:Body Weight / Q000187:drug effects; D002648:Child; D017315:Cilazapril / Q000031:analogs & derivatives; D003404:Creatinine / Q000097:blood; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D011724:Pyridazines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; D003404:Creatinine; C045980:cilazaprilat