Etravirine dispersible paediatric tablet has greater bioavailability when dispersed in water compared to swallowed whole
Etravirine (ETR) oral clearance in young children who swallowed the dispersible paediatric formulation was half that achieved with the tablet dispersed in water, according to results from IMPAACT P1090.
This finding in HIV positive children ages 1–6 years was presented at the 19th International Workshop on Clinical Pharmacology
The population pharmacokinetics (PK) of ETR have previously been described in adults, adolescents, and children 6 years and above but not in younger populations.
This study aimed to characterise the population PK and pharmacokinetic/pharmacodynamic (PK/PD) relationships of ETR in HIV positive children ages 1 to <6 years.
IMPAACT P1090 is a phase 1/2, multicentre, open-label study designed to evaluate the PK, optimal dose, safety, and tolerability of ETR in treatment-experienced children ages 1 to <6 years.
Participants received ETR with at least two other active antiretrovirals, one of which was a ritonavir-boosted protease inhibitor (PI/r). The study evaluated weight-based and weight-band based ETR doses.
A 12-hour intensive PK was performed two weeks after starting ETR and sparse samples were collected through week 48. Twenty-five children were included.
Children receiving ETR showed considerable inter-individual variability – similar to adults. Apparent oral clearance was 50% lower in children who swallowed the tablet whole versus dispersed in water. Weight and age were not significant predictors in the model. Although country and use of PI/r approached significance over-parameterisation of the model precluded their inclusion in the final model.
PK parameters were not associated with viral load at week 24.
The investigators suggested that this model can aid in comparisons of ETR PK parameters and dose selection in this younger population versus those previously reported for adults, adolescents, and children over 6 years.
Ibrahim M et al. Population pharmacokinetics/pharmacodynamics of etravirine in HIV-positive children ages 1-<6 years. 19th International Workshop on Clinical Pharmacology. Baltimore. 22–24 May 2018. Oral abstract 20.