Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment

作者：Vamshi Jogiraju, Elijah Weber, Jason T. Hindman, Steve West, John Ling, Martin S. Rhee, Sandhya Girish, Ramesh Palaparthy, Renu Singh · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2024 · DOI：10.1128/aac.01344-23 · 被引用次数：20 · 研究领域：HIV/AIDS drug development and treatment、HIV Research and Treatment、HIV/AIDS Research and Interventions

ABSTRACT Lenacapavir is a novel, first-in-class, multistage inhibitor of HIV-1 capsid function approved for the treatment of multidrug-resistant HIV-1 infection in combination with other antiretrovirals for heavily treatment-experienced people with HIV. Two Phase 1, open-label, parallel-group, single-dose studies assessed the pharmacokinetics (PK) of lenacapavir in participants with moderate hepatic impairment [Child–Pugh–Turcotte (CPT) Class B: score 7–9] or severe renal impairment [15 ≤ creatinine clearance (CLcr) ≤29 mL/min] to inform lenacapavir dosing in HIV-1-infected individuals with organ impairment. In both studies, a single oral dose of 300 mg lenacapavir was administered to participants with normal ( n = 10) or impaired ( n = 10) hepatic/renal function who were matched for age (±10 years), sex, and body mass index (±20%). Lenacapavir exposures [area under the plasma concentration–time curve from time 0 to infinity (AUC inf ) and maximum concentration (C max )] were approximately 1.47- and 2.61-fold higher, respectively, in participants with moderate hepatic impairment compared to those with normal hepatic function, whereas lenacapavir AUC inf and C max were approximately 1.84- and 2.62-fold higher, respectively, in participants with severe renal impairment compared to those with normal renal function. Increased lenacapavir exposures with moderate hepatic or severe renal impairment were not considered clinically meaningful. Lenacapavir was considered generally safe ...