Ideal Time to Conduct a Pharmacokinetic Investigation After Delivery to Fully Capture the Effect of Pregnancy on Drug Exposure.
Détails
ID Serval
serval:BIB_885488F32325
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Ideal Time to Conduct a Pharmacokinetic Investigation After Delivery to Fully Capture the Effect of Pregnancy on Drug Exposure.
Périodique
Open forum infectious diseases
ISSN
2328-8957 (Print)
ISSN-L
2328-8957
Statut éditorial
Publié
Date de publication
10/2024
Peer-reviewed
Oui
Volume
11
Numéro
10
Pages
ofae585
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
The World Health Organization is pushing to accelerate the study of new human immunodeficiency virus drugs in pregnant women. However, regulatory guidelines do not specify when to conduct pharmacokinetic studies in postpartum women. This knowledge gap carries the potential to jeopardize the outcomes and conclusions of clinical trials aiming to study the effect of pregnancy on drug exposure. We used physiologically based pharmacokinetic (PBPK) modeling along with clinical data to determine the time needed after delivery for drug exposure to return to prepregnancy levels.
A literature review was conducted to collect physiological parameters of pregnant and postpartum women. Regression analyses were performed to derive equations describing the parameters trajectory throughout pregnancy and post partum to inform our PBPK model. Published pharmacokinetic data in pregnant and postpartum women were used for the model verification. The PBPK model was subsequently applied to investigate pharmacokinetic changes throughout pregnancy and post partum.
In agreement with the clinical data the PBPK model was able to describe the different effects of pregnancy on drug exposure, with bictegravir showing the largest reduction in exposure (approximately 50%) during the third trimester while ritonavir and raltegravir showing the lowest (approximately 30%). The successfully verified PBPK model predicted that all evaluated antiretrovirals mostly return to prepregnancy exposure 4 weeks after delivery.
Pharmacokinetic investigations on hepatically cleared drugs should not be conducted before the fifth week after delivery to fully characterize the effect of pregnancy on drug exposure. Because physiological changes remain after delivery, early measurements can underestimate the pregnancy effect on pharmacokinetics, leading to suboptimal dosing recommendations during pregnancy.
A literature review was conducted to collect physiological parameters of pregnant and postpartum women. Regression analyses were performed to derive equations describing the parameters trajectory throughout pregnancy and post partum to inform our PBPK model. Published pharmacokinetic data in pregnant and postpartum women were used for the model verification. The PBPK model was subsequently applied to investigate pharmacokinetic changes throughout pregnancy and post partum.
In agreement with the clinical data the PBPK model was able to describe the different effects of pregnancy on drug exposure, with bictegravir showing the largest reduction in exposure (approximately 50%) during the third trimester while ritonavir and raltegravir showing the lowest (approximately 30%). The successfully verified PBPK model predicted that all evaluated antiretrovirals mostly return to prepregnancy exposure 4 weeks after delivery.
Pharmacokinetic investigations on hepatically cleared drugs should not be conducted before the fifth week after delivery to fully characterize the effect of pregnancy on drug exposure. Because physiological changes remain after delivery, early measurements can underestimate the pregnancy effect on pharmacokinetics, leading to suboptimal dosing recommendations during pregnancy.
Mots-clé
Hiv, antiretrovirals, pharmacokinetics, postpartum, pregnancy, HIV
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/10/2024 14:31
Dernière modification de la notice
20/12/2024 7:07