Establishment of a reference formulation for bioequivalence assessment of rifampicin-containing FDCs: an essential step towards improving tuberculosis treatment

• Published in: The international journal of tuberculosis and lung disease Vol. 9; no. 7; pp. 791 - 796
• Main Authors: ASHOKRAJ, Y, SINGH, I, KAUR, K. J, KOHLI, G, BHADE, S. R, VARMA, M. V. S, KAUL, C. L, PANCHAGNULA, R
• Format: Journal Article
• Language: English
• Published: Paris, France IUATLD 01.07.2005; Union internationale contre la tuberculose et les maladies respiratoires
• Subjects: Antibacterial agents; Antibiotics, Antitubercular - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - administration & dosage; Antitubercular Agents - pharmacokinetics; Area Under Curve; Bacterial diseases; Bioequivalence; Biological and medical sciences; Cross-Over Studies; DOTS; Drug Therapy, Combination; Ethambutol - administration & dosage; Ethambutol - pharmacokinetics; Fixed-Dose Combinations; General aspects; Human bacterial diseases; Humans; Infectious diseases; Isoniazid - administration & dosage; Isoniazid - therapeutic use; Medical sciences; Pharmacology. Drug treatments; Planification. Prevention (methods). Intervention. Evaluation; Public health. Hygiene; Public health. Hygiene-occupational medicine; rifampicin; Rifampin - pharmacokinetics; Therapeutic Equivalency; Tuberculosis; Tuberculosis - prevention & control; Tuberculosis and atypical mycobacterial infections; Human; Sanitary program; Bioequivalence; Respiratory disease; DOTS; Mycobacterial infection; Posology; Infection; fixed-dose combinations; Antibiotic; Rifampicin; Treatment; Tuberculosis; Formulation; Bacteriosis; Antituberculous agent; Antibacterial agent; Dose; Public health
• ISSN: 1027-3719; 1815-7920

SETTING: Selection of a reference product for bioequivalence studies of rifampicin (RMP) in prequalifying fixed-dose combinations (FDC) for worldwide distribution through the WHO is critical.OBJECTIVE: To investigate the feasibility of establishing FDC formulations as reference products for bioequivalence studies of RMP in prequalification programmes.DESIGN: A biostudy was conducted as an open, two-period randomised cross-over trial. Two three-drug FDCs containing RMP, isoniazid and ethambutol hydrochloride were administered to a group of 22 volunteers with a wash-out period of 1 week. Plasma samples were collected and analysed for the concentration of RMP and desacetyl-RMP, a major active metabolite of RMP, up to 24 h. Pharmacokinetic parameters of RMP were calculated: Cmax, AUC0-24, Tmax, kel and absorption efficiencies.RESULTS: No significant difference was observed between the administered formulations with respect to the major pharmacokinetic parameters Cmax, Tmax and AUC0-24 when evaluated by parametric (two-way ANOVA) and non-parametric (Hauschke's analysis) statistical analysis. The concentration of RMP falls within the reported acceptable therapeutic range.CONCLUSION: FDCs can be developed as a reference product for bioequivalence studies.