Pharmacokinetics and pharmacodynamics of trandolapril after repeated administration of 2 mg to young and elderly patients with mild-to-moderate hypertension.
The new angiotensin-converting enzyme (ACE) inhibitor trandolapril 2 mg was administered daily for 10 consecutive days to young (mean age +/- SEM 44.1 +/- 2.3 years; n = 10) and elderly (mean age +/- SEM 69.3 +/- 0.9 years; n = 14) patients with mild-to-moderate hypertension. All groups had similar baseline blood pressures: mean 164/100 mm Hg. Maximal plasma ACE inhibition on day 10 and residual inhibition 24 h after the last dose was the same, irrespective of age: young, 85.2 and 57.4%; elderly 89.1 and 59.8%, respectively. There was no difference between the results on day 1 for the young and elderly groups. The absorption of trandolapril was rapid (< 1 h in all groups). The peak plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were slightly higher in the older group, but the elimination half-life (t1/2) was the same, with no accumulation after repeat dosing. A steady-state plasma concentration of the active metabolite of trandolapril, trandolaprilat, was reached after 4 days in the two groups, with similar accumulation ratios (young, 1.48; elderly, 1.49). At steady state, the Cmax and AUC 0-24 h for trandolaprilat were similar in the two groups: young, 7.49 +/- 0.98 ng/ml and 82.27 +/- 6.95 ng/ml/h; elderly, 8.35 +/- 0.67 ng/ml/h and 96.75 +/- 5.67 ng/ml/h. Maximal reductions in systolic/diastolic blood pressures (at 6 h postdose) were -14.1%/-16.1% in young patients and -14.6%/-17.5% for the elderly. Significant blood pressure reduction persisted for 48 h after the last dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Arner
P
P
Karolinska Institutet, Institutionen för Medicin, Huddinge Sjukhus, Sweden.
Wade
A
A
Engfeldt
P
P
Mouren
M
M
Stepniewski
J P
JP
Sultan
E
E
Bryce
T
T
Lenfant
B
B
D000328:Adult; D000367:Age Factors; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D016037:Single-Blind Method
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril; D007703:Peptidyl-Dipeptidase A; C061095:trandolaprilat