Pharmacokinetics and safety of the abacavir/lamivudine/lopinavir/ritonavir fixed-dose granule formulation (4-in-1) in neonates : PETITE study

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dc.contributor.authorBekker, Adrieen_ZA
dc.contributor.authorRabie, Helenaen_ZA
dc.contributor.authorSalvadori, Nicolasen_ZA
dc.contributor.authorDu Toit, Samanthaen_ZA
dc.contributor.authorThan-in-at, Kanchanaen_ZA
dc.contributor.authorGroenewald, Marisaen_ZA
dc.contributor.authorAndrieux-Meyer, Isabelleen_ZA
dc.contributor.authorKumar, Mukeshen_ZA
dc.contributor.authorCressey, Ratchadaen_ZA
dc.contributor.authorNielsen, Jamesen_ZA
dc.contributor.authorCapparelli, Edmunden_ZA
dc.contributor.authorLallemant, Marcen_ZA
dc.contributor.authorCotton, Mark F.en_ZA
dc.contributor.authorCressey, Tim R.en_ZA
dc.date.accessioned2025-05-07T13:38:33Zen_ZA
dc.date.available2025-05-07T13:38:33Zen_ZA
dc.date.issued2022-03en_ZA
dc.descriptionCITATION: Bekker, A. et al. 2022. Pharmacokinetics and safety of the abacavir/lamivudine/lopinavir/ritonavir fixed-dose granule formulation (4-in-1) in neonates : PETITE study. JAIDS Journal of Acquired Immune Deficiency Syndromes,, 89(3):324-331, doi:10.1097/QAI.0000000000002871.en_ZA
dc.descriptionThe original publication is available at https://journals.lww.comen_ZA
dc.description.abstractABSTRACT: Background: Antiretroviral options for neonates (younger than 28 days) should be expanded. We evaluated the pharmacokinetics, safety, and acceptability of the "4-in-1" fixed-dose pediatric granule formulation of abacavir/lamivudine/lopinavir/ritonavir (30/15/40/10 mg) in neonates. Methods: The PETITE study is an ongoing phase I/II, open-label, single-arm, 2-stage trial conducted in South Africa. In stage 1, term neonates exposed to HIV on standard antiretroviral prophylaxis (nevirapine ± zidovudine) received single dose(s) of the 4-in-1 formulation, followed by intensive pharmacokinetic sampling and safety assessments. At each PK visit, blood was drawn after an observed dose at 1, 2, 4, 8, and 12 hours postdose. In this study, we have reported the planned interim pharmacokinetic and safety analysis after completion of the single-dose administration. Results: Sixteen neonates, with a median (range) birth weight of 3130 g (2790–3590 g), completed 24 pharmacokinetic visits. The 4-in-1 formulation imposed relatively high doses of abacavir [8.6 mg/kg (6.6–11.4)] and lamivudine [4.3 mg/kg (3.3–5.7)] but lower doses of lopinavir [11.5 mg/kg (8.8–15.2)]. The geometric means (GM, 90% CI) AUC0–12 of abacavir, lamivudine, and lopinavir were 29.87 (26.29–33.93), 12.61 (10.72–14.83), and 3.49 (2.13–5.72) µg.h/mL, respectively. Lopinavir GM AUC0–12 was below the predefined target (20–100 µg.h/mL), and ritonavir concentrations were only detectable in 4 of the 120 (3%) samples. No adverse events were related to study drugs. No neonate had difficulty swallowing the 4-in-1 formulation. Conclusions: The high doses of abacavir and lamivudine (in mg/kg) and AUCs were safe, and the formulation was well tolerated; however, lopinavir/ritonavir exposures were extremely low, preventing its use in neonates use in neonates. Alternative pediatric solid antiretroviral formulations must be studied in neonates.en_ZA
dc.description.sponsorshipUnitaiden_ZA
dc.description.versionPublisher's versionen_ZA
dc.format.extent8 pagesen_ZA
dc.identifier.citationCITATION: Bekker, A. et al. 2022. Pharmacokinetics and safety of the abacavir/lamivudine/lopinavir/ritonavir fixed-dose granule formulation (4-in-1) in neonates : PETITE study. JAIDS Journal of Acquired Immune Deficiency Syndromes,, 89(3):324-331, doi:10.1097/QAI.0000000000002871.en_ZA
dc.identifier.doi10.1097/QAI.0000000000002871en_ZA
dc.identifier.issn1077-9450 (online)en_ZA
dc.identifier.urihttps://scholar.sun.ac.za/handle/10019.1/131991en_ZA
dc.language.isoenen_ZA
dc.publisherWolters Kluweren_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subject.lcshPharmacokineticsen_ZA
dc.subject.lcshAntiretroviral agentsen_ZA
dc.subject.lcshNeonatologyen_ZA
dc.subject.lcshHIV infections -- Treatmenten_ZA
dc.titlePharmacokinetics and safety of the abacavir/lamivudine/lopinavir/ritonavir fixed-dose granule formulation (4-in-1) in neonates : PETITE studyen_ZA
dc.typeArticleen_ZA
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