title: Comparative bioavailability of rifampicin and isoniazid in fixed-dose combinations and single-drug formulations.
abstract: METHODS
  The bioavailability of rifampicin (RMP) decreases by ∼30% on interaction with isoniazid (INH) in stomach acid conditions, which can result in the development of drug resistance and treatment failure.
  
  
  OBJECTIVE
  To compare the bioavailability in healthy volunteers of five anti-tuberculosis fixed-drug combinations (FDCs) used in China (formulations A-E) containing RMP and INH against single-drug formulations taken as reference.
  
  
  METHODS
  Two- or three-period, two- or three-sequence crossover study of drugs.
  
  
  RESULTS
  Only RMP formulation E passed the bioequivalence criteria, with 90% confidence intervals for the log-transformed ratios of AUC₀₋₂₄, AUC₀₋∞, and Cmax of respectively 89.9-103.7, 89.6-102.2 and 87.7-107.9. For INH, formulations A, B, C and D passed the bioequivalence test, but not product E, where the 90%CIs of the log-transformed ratios of AUC₀₋₂₄, AUC₀₋∞, and Cmax were respectively 85.2-100.7, 85.2-100.7 and 73.8-100.9.
  
  
  CONCLUSIONS
  According to the results of the bioequivalence analysis carried out in this study, RMP formulations A, B, C and D were not within the acceptable range and only formulation E passed the bioequivalence criteria of 80-125%. In comparison, four-test INH formulations (A, B, C and D) were bioequivalent to the corresponding single-drug formulation, while product E failed in the bioequivalence criteria.
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, China.
authors.forename: L-H
authors.initials: LH
authors.lastname: Hao
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, China.
authors.forename: S-C
authors.initials: SC
authors.lastname: Guo
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, China.
authors.forename: C-C
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Fu
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Centers for Disease Control and Prevention, Beijing, China.
authors.forename: M-T
authors.initials: MT
authors.lastname: Chen
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Centers for Disease Control and Prevention, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Centers for Disease Control and Prevention, Beijing, China.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Chi
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, China.
authors.forename: W-J
authors.initials: WJ
authors.lastname: Nie
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumour Research Institute, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002681:China; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D004338:Drug Combinations; D013607:Tablets; D007538:Isoniazid; D012293:Rifampin