title: Plasma pooling methodology as a faster and cheaper tool to evaluate bioequivalence of rifampicin component of FDCs of antitubercular drugs.
abstract: Rifampicin is one of the most important first line drugs used in fixed dose combinations (FDCs) of antitubercular drugs. The chances of reduced bioavailability of rifampicin from FDCs necessitated its evaluation against standard formulations of individual drugs in bioequivalence studies. This study was undertaken to evaluate the importance of plasma pooling methodology as a rapid and cheaper tool to evaluate bioequivalence of rifampicin component of FDCs of antitubercular drugs. Plasma samples of volunteers obtained from bioequivalence studies were pooled according to volunteer and time-wise pooling. Area under the plasma concentration versus time curves (AUCs) of rifampicin was reduced in the pooled plasma samples when compared to the individual samples. However, the ratio of AUCs of FDCs to that of separate formulations was found to be comparable for both the individual samples and pooled samples data. Concentration-time profiles of rifampicin obtained after time-wise pooling were subjected to non-compartmental analysis for determination of pharmacokinetic parameters. Whereas bioequivalence estimates were determined using individual AUC values obtained from volunteer-wise pooling. Results indicated the possibility of using plasma pooling methodology in bioequivalence estimation of rifampicin to simplify and accelerate the registration process.
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, Phase-X, Mohali, Punjab 160062, India. panchagnula@yahoo.com
authors.forename: Ramesh
authors.initials: R
authors.lastname: Panchagnula
authors.forename: Ajay
authors.initials: A
authors.lastname: Sharma
authors.forename: Shrutidevi
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D000293:Adolescent; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001774:Blood Chemical Analysis / Q000191:economics / Q000379:methods; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012293:Rifampin / Q000097:blood* / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D000904:Antibiotics, Antitubercular; D002214:Capsules; D004338:Drug Combinations; D013607:Tablets; D012293:Rifampin