title: Minimum sample size and sampling time requirements for assessment of rifampicin bioequivalence from FDC formulations.
abstract: METHODS
  The WHO- and IUATLD-recommended protocol for rifampicin (RMP) bioequivalence utilises 20-22 volunteers and 8 h, whereas the requirement of other regulatory authorities is 12 volunteers with a 24 h sampling schedule. Differing sampling size and time requirements may change the outcome of RMP bioequivalence.
  
  
  OBJECTIVE
  To determine the minimal sample size and time required to assess RMP bioequivalence from FDC formulations.
  
  
  METHODS
  Bioequivalence studies were conducted that fulfilled the criteria of the WHO and Indian regulatory protocols. From earlier studies, retrospective pharmacokinetic evaluation, power of the test and bioequivalence limits were also calculated using 8-22 volunteers and sampling points of 8-24 h. Pharmacokinetic and statistical evaluations from three representative studies showing low, moderate and high intra-subject variability are given to determine minimum requirements for RMP bioequivalence.
  
  
  RESULTS
  It was found that a sampling schedule up to 8 h was sufficient to compare the absorption process of RMP. There was no influence of reduced sample size on bioequivalence estimates of RMP that showed low or moderate variability. However, in a study showing higher variation, a sample size of 14-16 subjects was found to be optimal.
  
  
  CONCLUSIONS
  It is possible to reduce the sample size requirement for determination of RMP bioequivalence using the WHO protocol.
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India.
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
authors.forename: K J
authors.initials: KJ
authors.lastname: Kaur
authors.forename: I
authors.initials: I
authors.lastname: Singh
authors.forename: S
authors.initials: S
authors.lastname: Bhade
authors.forename: C L
authors.initials: CL
authors.lastname: Kaul
authors.forename: R
authors.initials: R
authors.lastname: Panchagnula
mesh_terms: D000904:Antibiotics, Antitubercular / Q000592:standards*; D004338:Drug Combinations; D012293:Rifampin / Q000592:standards*; D018401:Sample Size; D013810:Therapeutic Equivalency; D013997:Time Factors
chemical_list: D000904:Antibiotics, Antitubercular; D004338:Drug Combinations; D012293:Rifampin