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- Title
Abacavir Drug Exposures in African Children Under 14 kg Using Pediatric Solid Fixed Dose Combinations According to World Health Organization Weight Bands.
- Authors
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; Team, DNDi Clinical; Cressey, Tim R; Punyawudho, Baralee; Musiime, Victor
- Abstract
Background The pharmacokinetics of abacavir (ABC) in African children living with HIV (CLHIV) weighing <14 kg and receiving pediatric fixed dose combinations (FDC) according to WHO weight bands dosing are limited. An ABC population pharmacokinetic model was developed to evaluate ABC exposure across different World Health Organization (WHO) weight bands. Methods Children enrolled in the LIVING study in Kenya and Uganda receiving ABC/lamivudine (3TC) dispersible tablets (60/30 mg) according to WHO weight bands. A population approach was used to determine the pharmacokinetic parameters. Monte Carlo simulations were conducted using an in silico population with demographic characteristics associated with African CLHIV. ABC exposures (AUC0–24) of 6.4–50.4 mg h/L were used as targets. Results Plasma samples were obtained from 387 children. A 1-compartment model with allometric scaling of clearance (CL/F) and volume of distribution (V/F) according to body weight best characterized the pharmacokinetic data of ABC. The maturation of ABC CL/F was characterized using a sigmoidal E max model dependent on postnatal age (50% of adult CL/F reached by 0.48 years of age). Exposures to ABC were within the target range for children weighing 6.0–24.9 kg, but children weighing 3–5.9 kg were predicted to be overexposed. Conclusions Lowering the ABC dosage to 30 mg twice daily or 60 mg once daily for children weighing 3–5.9 kg increased the proportion of children within the target and provided comparable exposures. Further clinical study is required to investigate clinical implications and safety of the proposed alternative ABC doses.
- Subjects
UGANDA; KENYA; WORLD Health Organization; AFRICANS; HIV-positive persons; COMPUTER simulation; BODY weight; ABACAVIR-lamivudine (Drug); PHARMACEUTICAL arithmetic; RESEARCH funding; RECEIVER operating characteristic curves; ABACAVIR; ENVIRONMENTAL exposure; CHILDREN
- Publication
Journal of the Pediatric Infectious Diseases Society, 2023, Vol 12, Issue 11, p574
- ISSN
2048-7193
- Publication type
Article
- DOI
10.1093/jpids/piad082