Accumulation of nifedipine after multiple doses.
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 ng h 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 ng h 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.
Lesko
L J
LJ
Hunter
J R
JR
Burgess
R C
RC
Rodgers
G P
GP
D000328:Adult; D001682:Biological Availability; D002849:Chromatography, Gas; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000378:metabolism*
D009543:Nifedipine