title: Relative bioavailability of rifampicin in four Chinese fixed-dose combinations compared with rifampicin in free combinations.
abstract: BACKGROUND
  Decreases in the bioavailability of rifampicin (RFP) can lead to the development of drug resistance and treatment failure. Therefore, we investigated the relative bioavailability of RFP from one four-drug fixed-dose combination (FDC; formulation A) and three two-drug FDCs (formulations B, C, and D) used in China, compared with RFP in free combinations of these drugs (reference), in healthy volunteers.
  
  
  METHODS
  Eighteen and twenty healthy Chinese male volunteers participated in two open-label, randomized two-period crossover (formulations A and C) or one three-period crossover (formulations B and D) study, respectively. The washout period between treatments was 7 days. Bioequivalence was assessed based on 90% confidence intervals, according to two one-sided t-tests. All analyses were done with DAS 3.1.5 (Mathematical Pharmacology Professional Committee of China, Shanghai, China).
  
  
  RESULTS
  Mean pharmacokinetic parameter values of RFP obtained for formulations A, B, C, and D products were 11.42 ± 3.41 μg/ml, 7.86 ± 5.78 μg/ml, 13.05 ± 6.80 μg/ml, and 16.18 ± 3.87 μg/ml, respectively, for peak plasma concentration (C max ), 91.43 ± 30.82 μg·h-1·ml-1 , 55.49 ± 37.58 μg·h-1·ml-1 , 96.50 ± 47.24 μg·h-1·ml-1 , 101.47 ± 33.07 μg·h-1·ml-1 , respectively, for area under the concentration-time curve (AUC 0-24 h ).
  
  
  CONCLUSIONS
  Although the concentrations of RFP for formulations A, C, and D were within the reported acceptable therapeutic range, only formulation A was bioequivalent to the reference product. The three two-drug FDCs (formulations B, C and D) displayed inferior RFP bioavailability compared with the reference (Chinese Clinical Trials registration number: ChiCTR-TTRCC-12002451).
authors: Hui
authors: H
authors: Zhu
authors: Shao-Chen
authors: SC
authors: Guo
authors: Lan-Hu
authors: LH
authors: Hao
authors: Cheng-Cheng
authors: CC
authors: Liu
authors: Bin
authors: B
authors: Wang
authors: Lei
authors: L
authors: Fu
authors: Ming-Ting
authors: MT
authors: Chen
authors: Lin
authors: L
authors: Zhou
authors: Jun-Ying
authors: JY
authors: Chi
authors: Wen
authors: W
authors: Yang
authors: Wen-Juan
authors: WJ
authors: Nie
authors: Department of Pharmacology, Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing 101149, China.
authors: Yu
authors: Y
authors: Lu
mesh_terms: D000328:Adult; D044466:Asian People; D001682:Biological Availability; D004338:Drug Combinations; D006801:Humans; D008297:Male; D012293:Rifampin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D012293:Rifampin