Steady state kinetics of a fatty alcohol-based slow-release nifedipine for once a day application

The linearity of the relationship between dose and plasma concentration of nifedipine has been investigated in healthy male and female subjects under steady state conditions following application of a fatty alcohol matrix slow release nifedipine (Aprical long, CAS 21829-25-4) formulation at a dose rate of 60, 90 and 120 mg once daily. Plasma concentrations showed a broad plateau associated with mean residence times exceeding 20 h. On Day 4 mean pre-dose nifedipine concentrations were 20.5, 24.9, 31.8 ng/ml and Cmax values were 42.3, 51.7 and 93.9 ng/ml for the 60, 90 and 120 mg dose, respectively (n = 15). After dose normalisation there was no significant difference (Wilcoxon matched pair test) in the mean AUCs. Adverse reactions, mainly headache and flushes, were observed at all dose levels but the frequency was not dose-dependent. In view of the demonstrated proportionality between dose and AUC and the long duration of the plateau plasma concentrations it is concluded that this slow release formulation is suitable for once daily administration at dose rates up to 120 mg daily.