logo
Science Portal
Copyright © Médecins Sans Frontières
v2.1.5153.produseast1
About MSF Science Portal
About
Contact Us
Frequently Asked Questions (FAQs)
Privacy Policy
Terms of Use
Copyright © Médecins Sans Frontières
v2.1.5153.produseast1
Abacavir drug exposures in African children under 14 kg using paediatric solid fixed dose combinations according to World Health Organization weight bands | Journal Article / Research | MSF Science Portal
Journal Article
|Research

Abacavir drug exposures in African children under 14 kg using paediatric solid fixed dose combinations according to World Health Organization weight bands

Chupradit S, Wamalwa DC, Maleche-Obimbo E, Kekitiinwa AR, Mwanga-Amumpaire J, Bukusi EA, Nyandiko WM, Mbuthia JK, Swanson A, Cressey TR, Punyawudho B, Musiime V
Download

Similar Content
Loading...
Loading...
Loading...
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 Emax 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.

Countries

Kenya Uganda

Subject Area

pediatricsHIV/AIDSpharmacokinetics

Languages

English
DOI
10.1093/jpids/piad082
Published Date
05 Oct 2023
PubMed ID
37798141
Journal
Journal of the Pediatric Infectious Diseases Society
Volume | Issue | Pages
Volume 12, Issue 11, Pages 574-580
Dimensions Badge