STUDY ON THE BIOEQUIVALENCE OF AN ORAL NIFEDIPINE FORMULATION AND A SUSTAINED-RELEASE REFERENCE PREPARATION AFTER SINGLE-DOSE AND REPEATED DOSES

Pharmacokinetic parameters of an oral formulation of nifedipine (CAS 2 1829-25-4, Corinfar(R), test preparation To a dragee with 10 mg nifedi pine) were compared with a reference preparation (fi a sustained relea se tablet with 20 mg nifedipine) in 16 healthy volunteers in a open tw o-way crossover study under the influence of ingestion of food A GC/MS method was used to analyse the serum samples. The estimation of bioeq uivalence was based on a nonparametric statistical procedure of analys is of variance. Both, the test preparation T and the reference prepara tion R are bioequivalent at steady state. The main pharmacokinetic par ameters (mean +/- standard deviation) used for the bioequivalence deci sion at steady state AUC(O-tau)(SS) (T: 351.4 +/- 161.0 ng . ml(-1). h , R: 345.5 +/- 146.8 ng . ml(-1). h), C-max(SS) (T: 67.3 +/- 29.5 ng . ml(-1); 66.9 +/- 33.0 ng . ml(-1)) and HVDSS (T: 3.8 +/- 1.3 h; R: 4. 2 +/- 1.8 h). The bioequivalence of rate and extent of absorption was proved for both preparations at steady state by assessing mean serum l evel curves as well as by statistics (90% confidence intervals) using the main pharmacokinetic parameters AUC(0-tau)(SS) (range: 0.84-1.02 p oint estimator 0.92), C-max(SS) (0.95-1.33, 1.15) HVDSS (0.72-0.98; 0. 82). The large interindividual variability of pharmacokinetics is typi cal of the drug and does not depend on the formulation used. No case o f severe disturbance of circulatory function or other adverse events w ith the duty to treat occurred during the study. No volunteer dropped out.