Predicting Drug Exposure During Pregnancy Using PBPK Models

On-Demand Webinar

Pregnancy is associated with numerous physiologic changes that can influence absorption, distribution, metabolism and excretion of medications. Moreover, the magnitude of these changes differs over the course of the pregnancy. For most medications, limited information is available about changes in drug disposition that can occur in pregnancy, yet most pregnant women are prescribed one or more medications. Accordingly, determining a safe and effective dose is challenging due to a lack of clinical studies involving pregnant women. Recent evidence suggests that physiologically based pharmacokinetic (PBPK) modeling is a potentially useful tool to characterize the pharmacokinetic profile of a medication in special populations such as pregnancy.

In this webinar, Dr. David Taft, Professor at Long Island University’s School of Pharmacy, will describe how the Simcyp pregnancy-PBPK model was used to predict systemic exposure during pregnancy for three probe medications: metformin, tacrolimus, and ostelamivir. These medications represent compounds with different ADME properties. Model simulations will be compared to clinical data in pregnant subjects in different trimesters of pregnancy as well as post-partum women. Dr. Taft will also show how the Simcyp Simulator can be used to correlate alterations in systemic exposure (Cmax, AUC) with various pregnancy-associated changes including organ blood flow, enzyme and transporter activity, and plasma protein levels. He will also discuss the future extensions of this research.

About Our Speaker

Dr. David R. Taft received his BS degree in pharmacy from the University of Rhode Island and his PhD from the University of Connecticut. Following completion of a fellowship in pharmacokinetics at the University of North Carolina School of Pharmacy, Dr. Taft joined the faculty at LIU in 1994. Dr. Taft teaches a variety of courses, particularly in pharmacokinetics, in both the professional program in pharmacy (PharmD) and the graduate programs (MS and PhD) in pharmaceutics. In addition, he provides instruction in physical pharmacy, pharmacy compounding, pharmacy math, and other courses. His primary research area is pharmacokinetics, with an emphasis on preclinical evaluation of drugs and drug candidates. Dr. Taft’s laboratory has collaborated with numerous companies in projects ranging from characterizing renal drug excretion in rat-kidney models to drug formulation evaluation in preclinical and clinical studies. Dr. Taft is past recipient of the AACP New Investigators Award, the Long Island University David Newton Award for Excellence in Teaching, the AAPS New Investigator Award in Pharmacokinetics, Pharmacodynamics and Drug Metabolism and the University of Connecticut School of Pharmacy Distinguished Alumni Award.

Pregnancy is associated with numerous physiologic changes that can influence absorption, distribution, metabolism and excretion of medications. Moreover, the magnitude of these changes differs over the course of the pregnancy. For most medications, limited information is available about changes in drug disposition that can occur in pregnancy, yet most pregnant women are prescribed one or more medications. Accordingly, determining a safe and effective dose is challenging due to a lack of clinical studies involving pregnant women. Recent evidence suggests that physiologically based pharmacokinetic (PBPK) modeling is a potentially useful tool to characterize the pharmacokinetic profile of a medication in special populations such as pregnancy.

In this webinar, Dr. David Taft, Professor at Long Island University’s School of Pharmacy, described how the Simcyp pregnancy-PBPK model was used to predict systemic exposure during pregnancy for two probe medications: tacrolimus and oseltamivir. These medications represent compounds with different ADME properties. Model simulations were compared to clinical data in pregnant subjects in different trimesters of pregnancy as well as post-partum women. Dr. Taft also showed how the Simcyp Simulator can be used to correlate alterations in systemic exposure (Cmax, AUC) with various pregnancy-associated changes including organ blood flow, enzyme and transporter activity, and plasma protein levels. Finally, he discussed the future extensions of this research.