THE EFFECT OF RIFAMPICIN ON THE PHARMACOKINETIC PARAMETERS OF NIFEDIPINE IN HEALTHY VOLUNTEERS

THE EFFECT OF RIFAMPICIN ON THE PHARMACOKINETIC PARAMETERS OF NIFEDIPINE IN HEALTHY VOLUNTEERS

Abstract:

Quality assessment of the three brands of nifedipine tablets/capsules were carried out. The identification tests, chemical assay and melting point method, determination showed that all the brands contained nifedipine as active ingredient. The results are in line with BP 1988 Addendun 1990 specifications for identification tests of nifedipine. Using U.V. spectroscopic methods, the U.V. spectra of all brands compared well with that of the reference with absorption maxima; at 206nm. 236nm and 344nm. The estimated total content of active ingredient of the brands of nifedipine using HPLC and U.V.- assay methods gave results which complied with the BP 1988 specification for the drug content (98 – 102%). The disintegration time for all the three brands of the nifedipine was less than 10 minutes. This result complied with BP 1988 specification for tab 1et/capsules disintegration time of not more than 15 minutes. The disssolution rate profiles of the three brands are similar. All the brands released more than 70% of their active ingredient in less than 30 minutes. These are within the limit specification by BP 1988 – of 45 minutes. The effect of a single oral dose of rifampicin 1200mg on the pharmacokinetics parameters of nifedipine lOmg (Capsules) was studied in a cross-over design in six healthy human volunteers (Age 28 ± 6.3 years old and weight of 60.67 ± 3.50). The pharmacokinetic parameters; such as tia(jg, Kabs , tlag , traax and Vd all showed no significant difference between the studies. Thus the absorption kinetics related parameters are not significantly different between the studies. However, those kinetic parameters related with metabolism and excretion kinetics showed significant differences. AUC0 – M (relative bioavailability) was decreased by 62.2% (573.4 Vs 205.25 mg.hr/ml) P < 0.0001: t½ el. was decreased by 67% (2.62 Vs 1.03 hr) P < 0.0001: ke,. was increased by 157% (0.260 Vs 0.670 hr”1 ) P < 0.0001; ClT was increased by 194% (17.33 Vs 50.17 ml/min.kg) P < 0.0001: Cma¥ decreased by 67% (173.23 Vs nidi 115.77 ng/ml ) P < 0.0001. This study showed that rifampicin increases the metabolism and elimination of nifedipine.

THE EFFECT OF RIFAMPICIN ON THE PHARMACOKINETIC PARAMETERS OF NIFEDIPINE IN HEALTHY VOLUNTEERS