The effect of ageing on the disposition of nifedipine and atenolol.
1. Healthy young and elderly volunteers received 20 mg nifedipine (slow release) orally for 2 weeks with concomitant dosing of atenolol 50 mg orally during the second week. 2. Drug kinetics and dynamics were compared between the groups after a single dose of nifedipine (day 1), after chronic dosing for 1 week (day 8), and following concomitant daily dosing of atenolol (day 15). 3. Plasma profiles of nifedipine were similar within each group on each of the 3 sampling days. The elderly group had higher plasma concentrations from about 6 h but there was no difference in the maximum concentrations achieved. The half-life in the elderly was significantly longer (8.8 +/- 0.9 h) compared with that in the young (5.8 +/- 1.1 h) (P less than 0.01). 4. Blood concentrations of atenolol were higher in the elderly at 12 and 24 h post-dose (P less than 0.001) and the AUC was greater than in the young (P less than 0.001). 5. Systolic blood pressure was reduced by nifedipine in both groups but to a greater extent in the elderly (P less than 0.01); differences in diastolic blood pressure were not significant. Blood pressure was reduced further by the addition of atenolol. Atenolol reduced the heart rate in all subjects.
Scott
M
M
Leicester General Hospital.
Castleden
C M
CM
Adam
H K
HK
Smith
R P
RP
Fitzsimons
T J
TJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001262:Atenolol / Q000009:adverse effects / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000493:pharmacokinetics*
D001262:Atenolol; D003404:Creatinine; D009543:Nifedipine