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Evaluation of bioequivalence of isoniazid and pyrazinamide in three and four drugs fixed dose combinations using WHO simplified protocol.
Pharmacol Res 2003; 48(4):383-7PR

Abstract

The reliable supply of quality drugs in the form of fixed dose combination (FDC) is an essential part of tuberculosis treatment. The objective of this investigation was to evaluate whether the World Health Organization (WHO) simplified screening protocol for the bioequivalence assessment of rifampicin can be used for the evaluation of other components of FDC so as to ensure the bioavailability of all drugs at tissue site. These bioequivalence studies were conducted on 20 and 22 healthy male volunteers for evaluation of three and four drugs FDC formulations, respectively. Both studies were conducted as randomized, open, crossover trials and sampling schedule was upto 8h according to WHO recommended protocol for evaluation of rifampicin bioequivalence. The bioequivalence of isoniazid and pyrazinamide were estimated using AUC(0-8), AUC(0-alpha), and C(max). FDC formulation was considered bioequivalent to separate formulations for isoniazid and pyrazinamide if bioequivalence limit fall in between 0.80 and 1.25. Bioequivalence estimates of AUC(0-8) and AUC(0-alpha) for isoniazid and all the three pharmacokinetic measures of pyrazinamide were within the acceptable limits, whereas C(max) of isoniazid from four drugs FDC was outside the limit when evaluated by two-way ANOVA. After evaluation of isoniazid and pyrazinamide based on their pharmacokinetics, it was found that C(max) is being affected by limited sampling time points of WHO protocol. Further, AUC was a robust parameter unaffected by sampling schedule adopted. The WHO simplified protocol for assessment of rifampicin is also suitable for evaluating bioequivalence of isoniazid and pyrazinamide from FDC formulations. However, for comparison of rate of absorption by means of C(max), careful evaluation of concentration-time profile along with pharmacokinetics is necessary before final judgment.

Authors+Show Affiliations

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, 160062 Punjab, S.A.S. Nagar, India. panchagnula@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12902209

Citation

Panchagnula, Ramesh, et al. "Evaluation of Bioequivalence of Isoniazid and Pyrazinamide in Three and Four Drugs Fixed Dose Combinations Using WHO Simplified Protocol." Pharmacological Research, vol. 48, no. 4, 2003, pp. 383-7.
Panchagnula R, Sancheti P, Rungta S, et al. Evaluation of bioequivalence of isoniazid and pyrazinamide in three and four drugs fixed dose combinations using WHO simplified protocol. Pharmacol Res. 2003;48(4):383-7.
Panchagnula, R., Sancheti, P., Rungta, S., Agrawal, S., & Kaul, C. L. (2003). Evaluation of bioequivalence of isoniazid and pyrazinamide in three and four drugs fixed dose combinations using WHO simplified protocol. Pharmacological Research, 48(4), pp. 383-7.
Panchagnula R, et al. Evaluation of Bioequivalence of Isoniazid and Pyrazinamide in Three and Four Drugs Fixed Dose Combinations Using WHO Simplified Protocol. Pharmacol Res. 2003;48(4):383-7. PubMed PMID: 12902209.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of bioequivalence of isoniazid and pyrazinamide in three and four drugs fixed dose combinations using WHO simplified protocol. AU - Panchagnula,Ramesh, AU - Sancheti,Pavankumar, AU - Rungta,Shradha, AU - Agrawal,Shrutidevi, AU - Kaul,Chaman Lal, PY - 2003/8/7/pubmed PY - 2004/6/17/medline PY - 2003/8/7/entrez SP - 383 EP - 7 JF - Pharmacological research JO - Pharmacol. Res. VL - 48 IS - 4 N2 - The reliable supply of quality drugs in the form of fixed dose combination (FDC) is an essential part of tuberculosis treatment. The objective of this investigation was to evaluate whether the World Health Organization (WHO) simplified screening protocol for the bioequivalence assessment of rifampicin can be used for the evaluation of other components of FDC so as to ensure the bioavailability of all drugs at tissue site. These bioequivalence studies were conducted on 20 and 22 healthy male volunteers for evaluation of three and four drugs FDC formulations, respectively. Both studies were conducted as randomized, open, crossover trials and sampling schedule was upto 8h according to WHO recommended protocol for evaluation of rifampicin bioequivalence. The bioequivalence of isoniazid and pyrazinamide were estimated using AUC(0-8), AUC(0-alpha), and C(max). FDC formulation was considered bioequivalent to separate formulations for isoniazid and pyrazinamide if bioequivalence limit fall in between 0.80 and 1.25. Bioequivalence estimates of AUC(0-8) and AUC(0-alpha) for isoniazid and all the three pharmacokinetic measures of pyrazinamide were within the acceptable limits, whereas C(max) of isoniazid from four drugs FDC was outside the limit when evaluated by two-way ANOVA. After evaluation of isoniazid and pyrazinamide based on their pharmacokinetics, it was found that C(max) is being affected by limited sampling time points of WHO protocol. Further, AUC was a robust parameter unaffected by sampling schedule adopted. The WHO simplified protocol for assessment of rifampicin is also suitable for evaluating bioequivalence of isoniazid and pyrazinamide from FDC formulations. However, for comparison of rate of absorption by means of C(max), careful evaluation of concentration-time profile along with pharmacokinetics is necessary before final judgment. SN - 1043-6618 UR - https://www.unboundmedicine.com/medline/citation/12902209/Evaluation_of_bioequivalence_of_isoniazid_and_pyrazinamide_in_three_and_four_drugs_fixed_dose_combinations_using_WHO_simplified_protocol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043661803001750 DB - PRIME DP - Unbound Medicine ER -