Age‐related changes in the pharmacokinetics and pharmacodynamics of nifedipine.

Abstract

1 The effects of age on the pharmacology of nifedipine were investigated in 11 young and six elderly normotensive volunteers. 2 Following 2.5 mg of nifedipine i.v. the plasma clearance of nifedipine was 348 ± 83 (s.d.) ml min-1 in the elderly compared with 519 ± 125 ml min'-in the young (P < 0.05) and the AUC in the elderly was significantly greater at 125 ± 28 ng mlF-I h compared with 83.9 ± 19 ng ml-' h (P < 0.05). The V1, was similar in both age groups.3 Following 10 mg oral sustained release nifedipine the AUC was 281 ± 64 ng ml-l h in the elderly compared with 136 ± 56 ng ml-' h in the young (P < 0.002) and Cmax in the elderly was significantly greater at 36.8 ± 11.8 ng ml-' compared with 22.3 ± 5.8 ng ml-' (P < 0.05). The trend towards an increased bioavailability in elderly subjects (36%) was supported by a significantly lower nitropyridine metabolite/nifedipine ratio in the elderly. 4 Absorption rate limited kinetics of the sustained release formulation were indicated by the prolonged tv2 compared with i.v. administration. In the elderly t½2 (oral) was significantly greater than in the young (elderly 6.7 ± 2.2 h, young 3.8 ± 1.4 h, P < 0.05). 5 Haemodynamic changes in the young were confined to a tachycardia following i.v. administration. In the elderly, supine BP fell significantly following both oral and i.v. nifedipine while the heart rate remained unchanged. 6 The results suggest that a reduction in first pass metabolism and clearance of nifedipine and impaired baroreceptor function in the elderly may both contribute to its increased hypotensive effect in this age group.

The pharmacokinetics of oral nifedipine‐a population study.

“…Assessment of the therapeutic implications of the polymorphic oxidation of nifedipine should include the following factors; a) polymorphism was not found at the commonly used dose of 10 mg, b) following 20 mg the interindividual variability in the 'good metaboliser' population (4.5 fold) was almost as great as that in the whole population (8 fold) (Kleinbloesem et al, 1984a) and c) there is a decrease in the metabolism of nifedipine with age, which will shift nearly all elderly subjects into the 'poor metaboliser' range (Robertson et al, 1987). These factors suggest that the polymorphic metabolism of nifedipine may be of academic interest but is of limited clinical importance.…”

“…However the two modes in that study did not differ with respect to age, gender, smoking habits and the use of oral contraceptives. Age profoundly alters the pharmacokinetics of nifedipine due to a decrease in clearance (Robertson et al, 1987), but neither gender (Lobo et al, 1986) nor smoking influence the AUC of nifedipine. Steroids may increase the ability of the human liver to metabolise nifedipine (Guengerich et al, 1986) a1-acid glycoprotein (51-76%) (Otto & Lesko, 1986) that it is difficult to envisage that the high AUC values arose from an increased binding to plasma proteins.…”

A novel vesicular transdermal delivery of nifedipine – preparation, characterization andin vitro/in-vivoevaluation

“…Its poor water solubility, high first pass metabolism (Hermann & Morselli, 1985), fast clearance rate may result in substantial intersubject pharmacokinetic variability, short elimination half-life (2 h) (Robertson et al, 1988), Adverse side-effects such as headache, flushing, dizziness, lethargy, bradycardia and ankle edema associated with plasma spikes are common.…”

Misuse of the standard error of the mean [letter]

“…are given, the reader can, by doubling them, at once estimate the ranges. The data of Robertson et al (1988), who made similar comparisons and give s.d.s, show a clear overlap between young and elderly subjects.…”

“…mean from the Journal. This should not be difficult, since the majority of authors -at least in the March 1988 issue -correctly use s. d. s. I am glad to see your predecessor among them (Robertson et al, 1988).…”