固定剂量复方片剂索磷布韦和来迪派韦（400/90mg）的仿制药与原研药的药物可互换性：基于健康埃及志愿者的参考比例平均生物等效性研究的应用。
Drug Interchangeability of Generic and Brand Products of Fixed Dose Combination Tablets of Sofosbuvir and Ledipasvir (400/90 mg): Employment of Reference Scaled Average Bioequivalence Study on Healthy Egyptian Volunteers.
机构信息
Clinical Pharmacy Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, Egypt.
Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt.
出版信息
Clin Drug Investig. 2018 May;38(5):439-448. doi: 10.1007/s40261-018-0622-8.
BACKGROUND AND OBJECTIVES
The purpose of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence and to investigate the pharmacokinetic properties of two formulations of fixed dose combination (FDC) tablet of sofosbuvir (SOF) and ledipasvir (LED) (400/90 mg) in 36 healthy Egyptian volunteers.
METHODS
The study was performed in single-dose, randomized-sequence, open-label, reference-replicated, 3-period crossover design (RTR, TRR, RRT), with a washout period of 2 weeks. A rapid and simple LC-MS/MS method was developed and validated for the simultaneous estimation of SOF and LED using eplerenone as an internal standard (IS).
RESULTS
The results showed that the 90% confidence intervals (CIs) for natural log-transformed ratios of C, AUC and AUC of SOF (89.95-115.31, 98.77-109.75 and 98.79-109.75) were within the RSABE acceptance limits. The 90% CIs for natural log-transformed ratios of C and AUC of LED (87.33-115.15 and 83.82-112.26) were within the FDA bioequivalence limits (80.00-125.00). In addition, the in vitro dissolution study was done and both formulations released > 85% of drug within 15 min in the proposed dissolution medium.
CONCLUSIONS
In conclusion, bioequivalence between the two fixed-dose combination products was demonstrated for both active ingredients.
背景和目的
本研究旨在应用参考标度平均生物等效性（RSABE）方法评估两种固定剂量复方（FDC）片剂索磷布韦（SOF）和来迪派韦（LED）（400/90mg）的生物等效性，并研究其药代动力学特性。在 36 名健康埃及志愿者中进行。
方法
该研究采用单剂量、随机序列、开放标签、参比复制、3 期交叉设计（RTR、TRR、RRT）进行，洗脱期为 2 周。开发并验证了一种快速简便的 LC-MS/MS 方法，用于同时使用依普利酮作为内标（IS）定量测定 SOF 和 LED。
结果
结果表明，SOF 的 C、AUC 和 AUC 的自然对数转化比值的 90%置信区间（CI）（89.95-115.31、98.77-109.75 和 98.79-109.75）均在 RSABE 可接受范围内。LED 的 C 和 AUC 的自然对数转化比值的 90%CI（87.33-115.15 和 83.82-112.26）均在 FDA 生物等效性范围内（80.00-125.00）。此外，还进行了体外溶出度研究，两种制剂在建议的溶出介质中在 15 分钟内释放了>85%的药物。
结论
总之，两种固定剂量复方产品的两种活性成分均表现出生物等效性。
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