Pharmacokinetics and Drug-Drug Interactions of Long-Acting Intramuscular Cabotegravir and Rilpivirine.

Combined antiretroviral treatments have significantly improved the morbidity and mortality related to HIV infection, thus transforming HIV infection into a chronic disease; however, the efficacy of antiretroviral treatments is highly dependent on the ability of infected individuals to adhere to life-long drug combination therapies. A major milestone in HIV treatment is the marketing of the long-acting intramuscular antiretroviral drugs cabotegravir and rilpivirine, allowing for infrequent drug administration, with the potential to improve adherence to therapy and treatment satisfaction. Intramuscular administration of cabotegravir and rilpivirine leads to differences in pharmacokinetics and drug–drug interaction (DDI) profiles compared with oral administration. A notable difference is the long elimination half-life with intramuscular administration, which reaches 5.6–11.5 weeks for cabotegravir and 13–28 weeks for rilpivirine, compared with 41 and 45 h, respectively, with their oral administration. Cabotegravir and rilpivirine have a low potential to cause DDIs, however these drugs can be victims of DDIs. Cabotegravir is mainly metabolized by UGT1A1, and rilpivirine is mainly metabolized by CYP3A4, therefore these agents are susceptible to DDIs with inhibitors, and particularly inducers of drug-metabolizing enzymes. Intramuscular administration of cabotegravir and rilpivirine has the advantage of eliminating DDIs occurring at the gastrointestinal level, however interactions can still occur at the hepatic level. This review provides insight on the intramuscular administration of drugs and summarizes the pharmacology of long-acting cabotegravir and rilpivirine. Particular emphasis is placed on DDI profiles after oral and intramuscular administration of these antiretroviral drugs.

联合抗逆转录病毒治疗显著改善了与艾滋病病毒感染相关的发病率和死亡率，从而将艾滋病病毒感染转变为一种慢性疾病；然而，抗逆转录病毒治疗的疗效在很大程度上取决于感染者坚持终身联合药物治疗的能力。艾滋病治疗的一个重要里程碑是长效肌肉注射抗逆转录病毒药物卡博特韦和利匹韦林的上市，其允许不频繁给药，有可能提高治疗依从性和治疗满意度。与口服给药相比，卡博特韦和利匹韦林的肌肉注射给药在药代动力学和药物相互作用（DDI）方面存在差异。一个显著的差异是肌肉注射给药的消除半衰期较长，卡博特韦为5.6 - 11.5周，利匹韦林为13 - 28周，而口服给药时分别为41小时和45小时。卡博特韦和利匹韦林引起药物相互作用的可能性较低，但这些药物可能会受到药物相互作用的影响。卡博特韦主要由UGT1A1代谢，利匹韦林主要由CYP3A4代谢，因此这些药物易与药物代谢酶的抑制剂，特别是诱导剂发生药物相互作用。卡博特韦和利匹韦林的肌肉注射给药具有消除胃肠道层面发生的药物相互作用的优势，但在肝脏层面仍可能发生相互作用。本综述深入探讨了药物的肌肉注射给药，并总结了长效卡博特韦和利匹韦林的药理学特性。特别强调了这些抗逆转录病毒药物口服和肌肉注射给药后的药物相互作用情况。