title: Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination.
abstract: BACKGROUND
  Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB).
  
  
  METHODS
  This study was conducted at a single centre--the Pfizer Clinical Research Unit in Singapore.
  
  
  OBJECTIVE
  To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination.
  
  
  METHODS
  In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (C(max)) and the area under plasma concentration-time curve (AUC).
  
  
  RESULTS
  Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for C(max) and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study.
  
  
  CONCLUSIONS
  The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: H F
authors.initials: HF
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: O'Gorman
authors.forename: P
authors.initials: P
authors.lastname: Crownover
authors.forename: A
authors.initials: A
authors.lastname: Naqvi
authors.forename: I
authors.initials: I
authors.lastname: Jafri
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005215:Fasting / Q000097:blood; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D012846:Singapore; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D004338:Drug Combinations; C469386:Myrin P; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin