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Population Pharmacokinetics of Pediatric Lopinavir/Ritonavir Oral Pellets in Children Living with HIV in Africa.
Chupradit, Suthunya; Wamalwa, Dalton C; Maleche-Obimbo, Elizabeth; Kekitiinwa, Adeodata R; Mwanga-Amumpaire, Juliet; Bukusi, Elizabeth A; Nyandiko, Winstone M; Mbuthia, Joseph K; Swanson, Alistair; Cressey, Tim R; Punyawudho, Baralee; Musiime, Victor.
Afiliación
  • Chupradit S; PhD's Degree Program in Pharmacy, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
  • Wamalwa DC; Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya.
  • Maleche-Obimbo E; Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya.
  • Kekitiinwa AR; Baylor College of Medicine Children's Foundation, Kampala, Uganda.
  • Mwanga-Amumpaire J; Epicentre, Mbarara, Uganda.
  • Bukusi EA; Centre for Microbiology Research, Kenya Medical Research Institute, Kisumu, Kenya.
  • Nyandiko WM; Department of Child Health and Paediatrics - Moi University, AMPATH and Moi Teaching and Referral Hospital, Eldoret, Kenya.
  • Mbuthia JK; Gertrude's Children's Hospital, Nairobi, Kenya.
  • Swanson A; Drugs for Neglected Diseases Initiative, Geneva, Switzerland.
  • Cressey TR; Drugs for Neglected Diseases Initiative, Bethesda, Maryland, USA.
  • Punyawudho B; Drugs for Neglected Diseases Initiative, Geneva, Switzerland.
  • Musiime V; Drugs for Neglected Diseases Initiative, Nairobi, Kenya.
Clin Pharmacol Ther ; 115(5): 1105-1113, 2024 May.
Article en En | MEDLINE | ID: mdl-38247190
ABSTRACT
Antiretroviral therapy for children living with HIV (CLHIV) under 3 years of age commonly includes lopinavir/ritonavir (LPV/r). However, the original liquid LPV/r formulation has taste and cold storage difficulties. To address these challenges, LPV/r oral pellets have been developed. These pellets can be mixed with milk or food for administration and do not require refrigeration. We developed the population pharmacokinetic (PK) model and assessed drug exposure of LPV/r oral pellets administered twice daily to CLHIV per World Health Organization (WHO) weight bands. The PK analysis included Kenyan and Ugandan children participating in the LIVING studies (NCT02346487) receiving LPV/r pellets (40/10 mg) and ABC/3TC (60/30 mg) dispersible tablets. Population PK models were developed for lopinavir (LPV) and ritonavir (RTV) to evaluate the impact of RTV on the oral clearance (CL/F) of LPV. The data obtained from the study were analyzed using nonlinear mixed-effects modeling approach. Data from 514 children, comprising a total of 2,998 plasma concentrations of LPV/r were included in the analysis. The LPV and RTV concentrations were accurately represented by a one-compartment model with first-order absorption (incorporating a lag-time) and elimination. Body weight influenced LPV and RTV PK parameters. The impact of RTV concentrations on the CL/F of LPV was characterized using a maximum effect model. Simulation-predicted target LPV exposures were achieved in children with this pellet formulation across the WHO weight bands. The LPV/r pellets dosed in accordance with WHO weight bands provide adequate LPV exposures in Kenyan and Ugandan children weighing 3.0 to 24.9 kg.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / Inhibidores de la Proteasa del VIH / Fármacos Anti-VIH Tipo de estudio: Prognostic_studies Límite: Child / Humans País/Región como asunto: Africa Idioma: En Revista: Clin Pharmacol Ther Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / Inhibidores de la Proteasa del VIH / Fármacos Anti-VIH Tipo de estudio: Prognostic_studies Límite: Child / Humans País/Región como asunto: Africa Idioma: En Revista: Clin Pharmacol Ther Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Estados Unidos