Year-end Sale % OFF 
Abstract
Background: Alterations in plasma protein concentrations in pregnant and postpartum individuals can influence antiretroviral (ARV) pharmacokinetics. Physiologically-based pharmacokinetic (PBPK) models can serve to inform drug dosing decisions in understudied populations. However, development of such models requires quantitative physiological information (e.g., changes in plasma protein concentration) from the population of interest.Objective: To quantitatively describe the time-course of albumin and α1-acid glycoprotein (AAG) concentrations in pregnant and postpartum women living with HIV.Methods: Serum and plasma protein concentrations procured from the International Maternal Pediatric Adolescent AIDS Clinical Trial Protocol 1026s (P1026s) were analyzed using a generalized additive modeling approach. Separate non-parametric smoothing splines were fit to albumin and AAG concentrations as functions of gestational age or postpartum duration.Results: The analysis included 871 and 757 serum albumin concentrations collected from 380 pregnant (~20 to 42 wks gestation) and 354 postpartum (0 to 46 wks postpartum) women, respectively. Thirty-six and 32 plasma AAG concentrations from 31 pregnant (~24 to 38 wks gestation) and 30 postpartum women (~2–13 wks postpartum), respectively, were available for analysis. Estimated mean albumin concentrations remained stable from 20 wks gestation to term (33.4 to 34.3 g/L); whereas, concentrations rapidly increased postpartum until stabilizing at ~42.3 g/L 15 wk after delivery. Estimated AAG concentrations slightly decreased from 24 wks gestation to term (53.6 and 44.9 mg/dL) while postpartum levels were elevated at two wks after delivery (126.1 mg/dL) and subsequently declined thereafter. Computational functions were developed to quantitatively communicate study results in a form that can be readily utilized for PBPK model development.Conclusion: By characterizing the trajectory of plasma protein concentrations in pregnant and postpartum women living with HIV, our analysis can increase confidence in PBPK model predictions for HIV antiretrovirals and better inform drug dosing decisions in this understudied population.
Highlights
The Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission recommends that all pregnant individuals1 living with HIV initiate or maintain antiretroviral (ARV) therapy throughout pregnancy regardless of plasma HIV RNA or CD4 count [1]
Considering the important influence that plasma protein binding exerts on systemic drug disposition, this study sought to [1] quantitatively describe the time-course of serum/plasma protein concentrations in pregnant and postpartum women living with HIV, [2] compare concentrations to values reported in pregnant and postpartum women without HIV infection, and [3] generate computational functions that describe the trajectory of serum/plasma protein concentrations in pregnant and postpartum women living with HIV to inform the prospective development of Physiologically based pharmacokinetic (PBPK) models
Our analysis evaluated serum and plasma protein concentrations procured from the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Protocol 1026s (P1026s), a multicenter, multi-arm, open-label prospective opportunistic study of ARV and tuberculosis medications in pregnant and postpartum women [20]
Summary
The Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission recommends that all pregnant individuals living with HIV initiate or maintain antiretroviral (ARV) therapy throughout pregnancy regardless of plasma HIV RNA or CD4 count [1]. Based pharmacokinetic (PBPK) modeling is an approach that has the potential to provide a priori predictions of drug disposition in understudied populations, such as pregnant individuals. Pregnant individuals living with HIV represent a demographically diverse population [9]. Quantitative physiological information on parameters influencing drug disposition in pregnant individuals living with HIV is limited. Alterations in plasma protein concentrations in pregnant and postpartum individuals can influence antiretroviral (ARV) pharmacokinetics. Physiologically-based pharmacokinetic (PBPK) models can serve to inform drug dosing decisions in understudied populations. Development of such models requires quantitative physiological information (e.g., changes in plasma protein concentration) from the population of interest
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
