Minimum sample size and sampling time requirements for assessment of rifampicin bioequivalence from FDC formulations
Abstract:SETTING: 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.
DESIGN: 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.
RESULT: 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.
CONCLUSION: It is possible to reduce the sample size requirement for determination of RMP bioequivalence using the WHO protocol.
Document Type: Regular Paper
Affiliations: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India
Publication date: 2005-11-01
The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.
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