Pharmacokinetics and tolerability of cabotegravir and rilpivirine long-acting intramuscular injections to the vastus lateralis (lateral thigh) muscles of healthy adult participants

作者：Kelong Han, Hakop Gevorkyan, Jafar Sadik Shaik, Herta Crauwels, Claudia Leemereise, Gilda Bontempo, Beta Win, Vasiliki Chounta, Ciara Seal, Rebecca DeMoor, Ronald D’Amico, William Spreen, Susan L. Ford · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2023 · DOI：10.1128/aac.00781-23 · 被引用次数：20 · 研究领域：HIV/AIDS drug development and treatment、HIV/AIDS Research and Interventions、HIV Research and Treatment

ABSTRACT Cabotegravir + rilpivirine administered via intramuscular gluteal injections is the first complete long-acting (LA) regimen approved for maintaining HIV-1 virologic suppression. The vastus lateralis (lateral) thigh muscle could be a potential alternative site of administration in circumstances such as injection site fatigue, intolerability, or contraindication for gluteal administration. Cabotegravir and rilpivirine pharmacokinetics and participant tolerability were evaluated following single intramuscular injections to the lateral thigh. Healthy adult participants received 4 weeks of daily oral cabotegravir (30 mg) and rilpivirine (25 mg), followed by a 10- to 14-day washout and single 3 mL intramuscular injections of cabotegravir LA 600 mg and rilpivirine LA 900 mg to the lateral thigh. Safety, tolerability, and pharmacokinetics were evaluated through 52 weeks post injection. Pharmacokinetic parameters were estimated using non-compartmental analysis. Fifteen participants (female at birth, n = 6) enrolled. Median age was 33 years. Median weight was 93.6 kg. Median body mass index was 31.4 kg/m 2 . One participant withdrew due to pregnancy after oral dosing before receiving an injection. Plasma concentrations at Weeks 4 and 8 were 15.4- and 5.3-fold above the protein-adjusted 90% inhibitory concentration for cabotegravir and 4.7- and 2.4-fold for rilpivirine, respectively. The most common injection site reactions were pain [28/28 (100%)], induration [15/28 (54%)], an...