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Pharmacokinetics and tolerability of cabotegravir and rilpivirine long-acting intramuscular injections to the vastus lateralis (lateral thigh) muscles of healthy adult participants
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dec 2023
The vastus lateralis (lateral thigh) muscle could be a potential alternative site of IM administration, helping to alleviate injection site fatigue or intolerability. Alternative IM injection sites could also be useful in instances of inaccessibility of the gluteal muscle (e.g., buttock implants or insufficient gluteal mass) or intermittently when gluteal injection is not ideal (e.g., prior to prolonged sitting). The vastus lateralis has been used as an injection location for the administration of other drugs, including epinephrine and vaccines, and is a common injection site in children (18, 19).
Conclusions
CAB and RPV PK data following a single IM injection into the lateral thigh muscle supported further evaluation of thigh IM administration in target populations of people living with HIV-1. The safety profiles of CAB LA and RPV LA IM injections to the lateral thigh muscle of healthy adult participants were comparable to the known safety profiles for CAB LA and RPV LA IM gluteal injections.
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/m2. 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%)], and swelling [12/28 (42%)]; 94% were Grade 1 or 2. Cabotegravir and rilpivirine plasma pharmacokinetic profiles observed in this study support further evaluation of thigh administration in target populations of people living with HIV-1. Tolerability of cabotegravir + rilpivirine LA intramuscular lateral thigh injections was similar to gluteal administration.
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