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 21829-25-4, Corinfar, test preparation T a dragee with 10 mg nifedipine) were compared with a reference preparation (R, a sustained release tablet with 20 mg nifedipine) in 16 healthy volunteers in a open two-way crossover study under the influence of ingestion of food. A GC/MS method was used to analyse the serum samples. The estimation of bioequivalence was based on a nonparametric statistical procedure of analysis of variance. Both, the test preparation T and the reference preparation R are bioequivalent at steady state. The main pharmacokinetic parameters (mean +/- standard deviation) used for the bioequivalence decision at steady state were AUC0- tau ss (T: 351.4 +/- 161.0 ng.ml-1.h; R: 345.5 +/- 146.8 ng.ml-1.h), Cmaxss (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 level curves as well as by statistics (90% confidence intervals) using the main pharmacokinetic parameters AUC0 - tau ss (range: 0.84-1.02 point estimator: 0.92), Cmaxss (0.95-1.33; 1.15) HVDss (0.72-0.98; 0.82). The large interindividual variability of pharmacokinetics is typical of the drug and does not depend on the formulation used. No case of severe disturbance of circulatory function or other adverse events with the duty to treat occurred during the study. No volunteer dropped out.
Tröger
U
U
Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany.
Martens
J
J
Meyer
F P
FP
Hoffmann
A
A
Terhaag
B
B
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D013810:Therapeutic Equivalency
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D009543:Nifedipine