Xu Lianhong, Desai Manoj C
Gilead Sciences Inc, Department of Medicinal Chemistry, 333 Lakeside Drive, Foster City, CA 94404, USA.
Curr Opin Investig Drugs. 2009 Aug;10(8):775-86.
The HIV protease inhibitor (PI) ritonavir is a potent, mechanism-based inhibitor of cytochrome P450 CYP3A4, an enzyme that is responsible for metabolizing most HIV PIs. Ritonavir is therefore able to enhance the effectiveness of PI treatment by reducing the pill burden, simplifying dosing regimens and improving therapy adherence. Ritonavir coadministration improves the pharmacokinetic (PK) profiles of concomitant PIs, and represents a cornerstone of PI-containing regimens. However, ritonavir is associated with undesirable side effects, such as gastrointestinal problems and lipid disturbances. This review summarizes salient features and limitations associated with the use of ritonavir as a PK enhancer, and briefly describes novel PK enhancers that are in development.
人类免疫缺陷病毒蛋白酶抑制剂（PI）利托那韦是一种强效的、基于机制的细胞色素P450 CYP3A4抑制剂，该酶负责代谢大多数HIV蛋白酶抑制剂。因此，利托那韦能够通过减轻服药负担、简化给药方案和提高治疗依从性来增强PI治疗的效果。利托那韦联合给药可改善同时使用的PI的药代动力学（PK）特征，是含PI治疗方案的基石。然而，利托那韦会带来不良副作用，如胃肠道问题和脂质紊乱。本综述总结了与使用利托那韦作为PK增强剂相关的显著特征和局限性，并简要描述了正在研发的新型PK增强剂。
