Tags

Type your tag names separated by a space and hit enter

Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels.
Int J Pharm 2004; 276(1-2):41-9IJ

Abstract

Fixed dose combination (FDC) formulations became popular in the treatment of tuberculosis (TB) because of the better patient compliance, reduced risk of monotherapy and emergence of drug resistance in contrast to treatment with separate formulations of two to four first-line drugs. However, its successful implementation in national programs is limited by probable bioinequivalency of rifampicin if present in FDC form. In this regard, World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. Hence, bioequivalence study of four drug FDC tablet was conducted using 22 healthy male volunteers according to WHO recommended protocol to determine bioavailability of rifampicin, isoniazid and pyrazinamide compared to standard separate combination at the same dose level. The study was designed as two period, two treatment crossover experiment with a washout period of 1 week. Bioequivalence of rifampicin was estimated by plasma and urinary method for both rifampicin and its active metabolite, des-acetyl rifampicin whereas isoniazid and pyrazinamide were estimated from plasma. Mean concentration time profiles and all the pharmacokinetic parameters of rifampicin, isoniazid and pyrazinamide from FDC tablet were comparable to individual formulations and passed the bioequivalence test with power of the test above 95%. Further, bioequivalence of both rifampicin and isoniazid shows that in vitro interaction of rifampicin and isoniazid is clinically insignificant. Thus, it was concluded that FDC formulation is bioequivalent for rifampicin, isoniazid and pyrazinamide and ensures the successful treatment of TB without compromising therapeutic efficacy of any of these components of anti-TB therapy.

Authors+Show Affiliations

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar 160062, Punjab, India.

Pub Type(s)

Clinical Trial
Comparative Study
Controlled Clinical Trial
Journal Article

Language

eng

PubMed ID

15113612

Citation

Agrawal, Shrutidevi, et al. "Comparative Bioavailability of Rifampicin, Isoniazid and Pyrazinamide From a Four Drug Fixed Dose Combination With Separate Formulations at the Same Dose Levels." International Journal of Pharmaceutics, vol. 276, no. 1-2, 2004, pp. 41-9.
Agrawal S, Singh I, Kaur KJ, et al. Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels. Int J Pharm. 2004;276(1-2):41-9.
Agrawal, S., Singh, I., Kaur, K. J., Bhade, S. R., Kaul, C. L., & Panchagnula, R. (2004). Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels. International Journal of Pharmaceutics, 276(1-2), pp. 41-9.
Agrawal S, et al. Comparative Bioavailability of Rifampicin, Isoniazid and Pyrazinamide From a Four Drug Fixed Dose Combination With Separate Formulations at the Same Dose Levels. Int J Pharm. 2004 May 19;276(1-2):41-9. PubMed PMID: 15113612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels. AU - Agrawal,Shrutidevi, AU - Singh,Inderjit, AU - Kaur,Kanwal Jit, AU - Bhade,Shantaram R, AU - Kaul,Chaman Lal, AU - Panchagnula,Ramesh, PY - 2003/10/21/received PY - 2004/01/25/revised PY - 2004/02/07/accepted PY - 2004/4/29/pubmed PY - 2004/8/18/medline PY - 2004/4/29/entrez SP - 41 EP - 9 JF - International journal of pharmaceutics JO - Int J Pharm VL - 276 IS - 1-2 N2 - Fixed dose combination (FDC) formulations became popular in the treatment of tuberculosis (TB) because of the better patient compliance, reduced risk of monotherapy and emergence of drug resistance in contrast to treatment with separate formulations of two to four first-line drugs. However, its successful implementation in national programs is limited by probable bioinequivalency of rifampicin if present in FDC form. In this regard, World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. Hence, bioequivalence study of four drug FDC tablet was conducted using 22 healthy male volunteers according to WHO recommended protocol to determine bioavailability of rifampicin, isoniazid and pyrazinamide compared to standard separate combination at the same dose level. The study was designed as two period, two treatment crossover experiment with a washout period of 1 week. Bioequivalence of rifampicin was estimated by plasma and urinary method for both rifampicin and its active metabolite, des-acetyl rifampicin whereas isoniazid and pyrazinamide were estimated from plasma. Mean concentration time profiles and all the pharmacokinetic parameters of rifampicin, isoniazid and pyrazinamide from FDC tablet were comparable to individual formulations and passed the bioequivalence test with power of the test above 95%. Further, bioequivalence of both rifampicin and isoniazid shows that in vitro interaction of rifampicin and isoniazid is clinically insignificant. Thus, it was concluded that FDC formulation is bioequivalent for rifampicin, isoniazid and pyrazinamide and ensures the successful treatment of TB without compromising therapeutic efficacy of any of these components of anti-TB therapy. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/15113612/Comparative_bioavailability_of_rifampicin_isoniazid_and_pyrazinamide_from_a_four_drug_fixed_dose_combination_with_separate_formulations_at_the_same_dose_levels_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378517304001346 DB - PRIME DP - Unbound Medicine ER -