A Pharmacokinetic Dose-Optimization Study of Cabotegravir and Bictegravir in a Mouse Pregnancy Model

Animal pregnancy models can be useful tools to study HIV antiretroviral safety and toxicity and to perform mechanistic studies that are not easily performed in humans. Utilization of clinically relevant dosing in these models improves the relevance of the findings. Cabotegravir and bictegravir are n...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutics 2022-08, Vol.14 (9), p.1761
Main Authors: Mohan, Haneesha, Atkinson, Kieran, Watson, Birgit, Brumme, Chanson J, Serghides, Lena
Format: Article
Language:English
Subjects:
Amniotic fluid
Analysis
bictegravir
Birth defects
Breastfeeding & lactation
cabotegravir
Drug dosages
Drug resistance
High performance liquid chromatography
HIV
HIV antiretrovirals
Human immunodeficiency virus
INSTI
mouse
Pharmacokinetics
Plasma
Pregnancy
Prescription drugs
Prevention
Rodents
Surveillance
Womens health
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Animal pregnancy models can be useful tools to study HIV antiretroviral safety and toxicity and to perform mechanistic studies that are not easily performed in humans. Utilization of clinically relevant dosing in these models improves the relevance of the findings. Cabotegravir and bictegravir are new integrase strand transfer inhibitors (INSTIs), recently approved for the treatment of people living with HIV. Studies of these drugs in pregnancy are very limited. The objective of this study was to perform a dose-optimization study of cabotegravir and bictegravir in a mouse pregnancy model with the goal of determining the dose that would yield plasma drug concentrations similar those observed in humans. Pregnant mice were administered increasing doses of cabotegravir or bictegravir in combination with emtricitabine and tenofovir by oral gavage from gestational day 11.5 to 15.5. Drug concentrations in the maternal plasma at 1 h and 24 h post drug administration and in the amniotic fluid at 1 h post drug administration were determined using high-performance liquid chromatography coupled with tandem mass spectrometry. A review of cabotegravir and bictegravir human pharmacokinetic studies are also reported. We hope these data will encourage studies of HIV antiretroviral safety/toxicity and mechanistic studies in animal pregnancy models.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14091761