Physiologically based pharmacokinetic model combined with a clinical lactation study to determine doravirine concentrations in human breastmilk.

ABSTRACT:

Aims

To determine breastmilk concentrations of doravirine via PBPK modelling in combination with a clinical lactation study. As women living with HIV are not able to cease antiretroviral therapy during lactation, it is necessary to establish drug transfer into breastmilk to determine exposure of the infant to antiretroviral drugs and potential risk of drug-induced toxicity.

Methods

PBPK modelling was performed with Simcyp v22 with the lactation module as an add-on. Model predictions were compared with observed data, and model performance was considered adequate if predicted: observed ratios for AUC_0-24, C_max and half-life fell between 0.7 and 1.43. Observed data originated from a study performed in healthy, lactating women from whom a full pharmacokinet

SUBMITTER: van der Wekken-Pas L 

PROVIDER: S-EPMC12930008 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature