Agrawal S, Kaur K J, Singh I, Bhade S R, Kaul C L, Panchagnula R
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Nagar, India.
Int J Tuberc Lung Dis. 2005 Jan;9(1):75-80.
To promote the quality assurance of fixed-dose combination (FDC) formulations, the World Health Organization (WHO) has prepared a convenient simplified protocol for the determination of rifampicin (RMP) bioequivalence. During the development of this protocol, it was proved that sampling time up to 8 h can determine the rate and extent of RMP absorption. However, this protocol utilises 20 volunteers in contrast to other local regulatory requirements of a minimum of 12 volunteers. The different sample sizes utilised in these protocols may affect the sensitivity of the bioequivalence outcome.
To determine the effect of sampling size and schedule on RMP bioequivalence when two different protocols are used.
A bioequivalence trial was conducted with a study design of 20 volunteers and 24 h sampling time, which fulfils the requirements of both the WHO and Indian regulatory protocols. Pharmacokinetic and statistical analysis was done by stepwise reduction in sample size and schedule.
Bioequivalence limits of RMP were unaffected by a reduced sample size of 12 volunteers and 8 h sampling time.
Minimising sample size after validation for borderline and poor quality FDC formulations can further reduce the cost of conducting bioequivalence trials.
为提高固定剂量复方制剂（FDC）的质量保证，世界卫生组织（WHO）制定了一种简便的简化方案，用于测定利福平（RMP）的生物等效性。在制定该方案的过程中，已证明长达8小时的采样时间能够确定RMP的吸收速率和程度。然而，与其他地方监管要求至少12名志愿者相比，该方案使用了20名志愿者。这些方案中使用的不同样本量可能会影响生物等效性结果的敏感性。
确定使用两种不同方案时，样本量和采样时间表对RMP生物等效性的影响。
进行了一项生物等效性试验，采用20名志愿者和24小时采样时间的研究设计，该设计符合WHO和印度监管方案的要求。通过逐步减少样本量和采样时间表进行药代动力学和统计分析。
RMP的生物等效性限度不受12名志愿者的减少样本量和8小时采样时间的影响。
对于临界质量和低质量的FDC制剂，在验证后将样本量最小化可进一步降低进行生物等效性试验的成本。
