Related Experiment Video
Updated: Jul 26, 2025

Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
Published on: September 10, 2018
Quantification of sertraline maternal/fetal ratio and amniotic fluid concentration using a pregnancy physiologically
David Lartey1,2, Danielle Jateng1,2, Miao Li3
1Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Aims:
Selective serotonin reuptake inhibitors (SSRIs) are indicated for a variety of psychiatric conditions which may require treatment during pregnancy. Knowledge of appropriate SSRI dosages that maintain maternal therapeutic benefit and minimize fetal risk are needed. Assessment of fetal exposure to drugs is challenging since sampling is often limited to a single concentration from the umbilical cord at delivery. Physiologically based pharmacokinetic (PBPK) modelling provides a non-invasive approach to quantify exposure in pregnancy.
Methods:
We incorporated sertraline clearances mediated by passive diffusion, placental efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) into our previously published pregnancy PBPK model for sertraline. Simulations were performed for various sertraline doses (25-200 mg) at 40 weeks gestational age to predict the minimum (Cmin), maximum (Cmax) and average (Cavg) sertraline maternal and fetal plasma concentrations and evaluated them against observed maternal and cord concentrations obtained at delivery from five clinical studies.
Results:
The accuracy of the PBPK predictions as indicated by the average fold error (AFE) value for Cmax, Cmin and Cavg for maternal plasma sertraline concentrations at delivery was 1.7, 1.2 and 1.4, respectively. The AFE for the Cmax, Cmin and Cavg for cord blood sertraline concentration at delivery was 1.2, 1 and 1.1, respectively. The AFE for cord-maternal sertraline concentration ratio at delivery for Cmax, Cmin and Cavg was 0.7, 0.9 and 0.8, respectively.
Conclusions:
The PBPK model we developed may serve as a guide for maternal sertraline dose adjustment during pregnancy considering changes in exposures for both mother and fetus.
More Related Videos
08:08Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model
Published on: June 18, 2013
08:22Quantification of Ethanol Levels in Zebrafish Embryos Using Head Space Gas Chromatography
Published on: February 11, 2020
Related Concept Videos
Physiological Pharmacokinetic Models: Assumption with Protein Binding
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion,...
Pharmacokinetic Models: Comparison and Selection Criterion
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Model Approaches for Pharmacokinetic Data: Physiological Models
Teratogenicity