The effect of ageing on the disposition of nifedipine and atenolol.

Abstract

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.

Single Dose and Steady-State Pharmacokinetic Profiles of Nifedipine GITS Tablets in Healthy Elderly and Young Volunteers

“…Inspection of the mean plasma nifedipine concentration vs time profiles at steady-state reveals an interesting difference in the apparent rate of elimination after 24 hours. Concentrations decline rapidly in the group of young subjects, whereas the decline is more gradual in the elderly group, a well-documented phenomenon (Robertson et al 1988;Scott et al 1988), which is reflected as a 12% decrease in clearance of nifedipine in the elderly.…”

“…Although several pharmacokinetic studies on nifedipine retarded-release formulations have concentrated on young, healthy subjects (A vgerinos & Gorrod 1990;Debbas et al 1986;Kohri et al 1987;Leucuta 1988;Ohnishi et al 1987;Saano et al 1989) or hypertensive patients (Murdoch & Brogden 1991), the possibility of age-related changes in nifedipine pharmacokinetics have only recently been investigated (Robertson et al 1988;Scott et al 1988). The present study was carried out to compare the acute and steady-state pharmacokinetics of the nifedipine GITS tablet formulation in healthy elderly and young volunteers, and to evaluate the safety of nifedipine GITS in these populations.…”

Calcium channel antagonists: part VI: Clinical pharmacokinetics of first and second-generation agents

“…The elimination half-life of nifedipine is apparently dependent upon the dosage form in which it is administered, with half-lives of 3 hours, 5 to 11 hours, and 1.5 hours measured after oral capsule, oral tablet, and intravenous administration, respectively [2]. However, the slow-release preparation of nifedipine has a much lower absorption than elimination time and therefore the longer half-life really reflects a delayed rate of absorption, which is termed flip-flop kinetics [28]. The total systemic clearance of nifedipine from the plasma is about 0.5 1/kg/hour (range 0.4 to 0.6), which is primarily due to hepatic metabolism, and the volume of distribution about 0.6 to 1.4 l/kg, showing significant distribution to the tissues [2].…”

“…This difference, together with the fear of abrupt peripheral vasodilation with cerebral underperfusion, suggests that the initial dose in elderly patients should be 5 mg and not 10 mg (the 5-rag capsule form is available in many countries, otherwise cut a 10-mg capsule in half). Using the slowrelease preparation, the elimination half-life varies from about 4 to 6 hours in young patients to 7 to 9 hours in the elderly [28,38]. In elderly patients, nifedipine slow-release has been used in doses of 20 to 60 mg twice daily [39].…”

Amlodipin versus Nifedipin retard Eine randomisierte Doppelblindstudie zum Vergleich der Langzeitwirksamkeit und Verträglichkeit von Amlodipin und Nifedipin retard in der Monotherapie der chronisch stabilen Angina pectoris

“…Die größere Schwankungsbreite der Plasmakonzentration von Nifedipin retard wird durch die höhere Peak-through-Ratio (definiert als Quotient der höchsten und niedrigsten Plasmakonzentration im Dosierungsintervall) reflektiert. Während die Plasmakonzentration von Amlodipin im Steady State 24 Stunden nach der letzten Einnahme immer noch 60% des Maximalwerts beträgt und somit die Peak-through-Ratio mit 1,5 gering ist [2], beträgt sie bei Nifedipin retard rund 10 [17]. Die günstigen pharmakokinetischen Eigenschaften des lang wirksamen Amlodipins ermöglichen dadurch eine gleich bleibendere Wirkung im gesamten Dosierungsintervall als Nifedipin retard.…”