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

BACKGROUND: The pharmacokinetics of abacavir (ABC) in African children living with HIV (CLHIV) weighing

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 one-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 yrs. 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.

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