Biopharmaceutics, Product Value Enhancement, Pharmaceutical Sciences and Clinical Supply, Merck Sharp & Dohme Corp., West Point, Pennsylvania 19486, USA.
AAPS J. 2012 Sep;14(3):646-55. doi: 10.1208/s12248-012-9378-x. Epub 2012 Jun 9.
Fixed-dose combination (FDC) products are becoming a popular treatment option because of increased patient compliance and convenience, improved clinical effectiveness, and reduced cost to the patient, among several other reasons. A commonly applied approach for approval of a FDC product is demonstrating bioequivalence between the FDC and co-administration of individual mono-products, provided that there is adequate safety and efficacy data for co-administration of the individual agents. However, achieving bioequivalence between the FDC and individual mono-products can be very challenging, and sometimes not possible since combining multiple active ingredients, especially insoluble molecules, in a single drug product could complicate its biopharmaceutical and pharmacokinetic behavior. In this review, some of the major challenges often encountered while assessing bioequivalence during FDC development will be presented along with discussion of future opportunities to facilitate FDC development and approval.
固定剂量组合（FDC）产品因其提高了患者的顺应性和便利性、改善了临床疗效、降低了患者的成本等诸多原因，成为一种受欢迎的治疗选择。通常，批准 FDC 产品的一种常用方法是证明 FDC 与个体单产品联合使用之间的生物等效性，前提是联合使用个体药物具有足够的安全性和疗效数据。然而，实现 FDC 与个体单产品之间的生物等效性可能极具挑战性，有时甚至不可能，因为将多种活性成分（特别是不溶性分子）组合在单一药物产品中可能会使其生物药剂学和药代动力学行为复杂化。在这篇综述中，将介绍在 FDC 开发过程中评估生物等效性时经常遇到的一些主要挑战，并讨论促进 FDC 开发和批准的未来机会。
