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Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations.
Int J Clin Pharmacol Ther 2002; 40(10):474-81IJ

Abstract

Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels.

Authors+Show Affiliations

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Nagar, Punjab, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

12395981

Citation

Agrawal, S, et al. "Bioequivalence Assessment of Rifampicin, Isoniazid and Pyrazinamide in a Fixed Dose Combination of Rifampicin, Isoniazid, Pyrazinamide and Ethambutol Vs. Separate Formulations." International Journal of Clinical Pharmacology and Therapeutics, vol. 40, no. 10, 2002, pp. 474-81.
Agrawal S, Singh I, Kaur KJ, et al. Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations. Int J Clin Pharmacol Ther. 2002;40(10):474-81.
Agrawal, S., Singh, I., Kaur, K. J., Bhade, S. R., Kaul, C. L., & Panchagnula, R. (2002). Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations. International Journal of Clinical Pharmacology and Therapeutics, 40(10), pp. 474-81.
Agrawal S, et al. Bioequivalence Assessment of Rifampicin, Isoniazid and Pyrazinamide in a Fixed Dose Combination of Rifampicin, Isoniazid, Pyrazinamide and Ethambutol Vs. Separate Formulations. Int J Clin Pharmacol Ther. 2002;40(10):474-81. PubMed PMID: 12395981.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations. AU - Agrawal,S, AU - Singh,I, AU - Kaur,K J, AU - Bhade,S R, AU - Kaul,C L, AU - Panchagnula,R, PY - 2002/10/25/pubmed PY - 2003/3/22/medline PY - 2002/10/25/entrez SP - 474 EP - 81 JF - International journal of clinical pharmacology and therapeutics JO - Int J Clin Pharmacol Ther VL - 40 IS - 10 N2 - Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels. SN - 0946-1965 UR - https://www.unboundmedicine.com/medline/citation/12395981/Bioequivalence_assessment_of_rifampicin_isoniazid_and_pyrazinamide_in_a_fixed_dose_combination_of_rifampicin_isoniazid_pyrazinamide_and_ethambutol_vs__separate_formulations_ L2 - https://medlineplus.gov/tuberculosis.html DB - PRIME DP - Unbound Medicine ER -