Accumulation of nifedipine after multiple doses

Publisher Website
Google Scholar
Abstract
The single and multiple dose pharmacokinetics of oral nifedipine capsules, 10 mg, have been examined in five patients with peripheral vasospasm. After a single dose, nifedipine was rapidly absorbed in three and slowly absorbed in two patients. Mean bioavailability parameters included a tmax of 2.9 h, a Cmax of 33.3 ng ml−1 and a AUC0–8 h of 113.3 ngh ml−1. After multiple dosing with either 10 or 20 mg every 8 h for 10 days the mean tmax at steady state was 2.1 h while the mean dose-corrected (to 10 mg) Cmax and AUC0–8 h were 51.9 ng ml−1 and 146.9 ngh ml−1, respectively. The mean elimination rate constant was 0.173 h−1 after both single and multiple doses. The mean extent of accumulation of nifedipine, defined as the ratio of AUC0–8 h (steady state)/AUC0–8 h (single dose), was 1.3; we concluded that nifedipine accumulates in the body when it is administered every 8 h. This should be taken into account when predicting steady state serum concentrations and haemodynamic effects of nifedipine from single dose kinetic data.