Physiologically based pharmacokinetic model of midazolam disposition during pregnancy.

Marilee A Andrew, Mary F Hebert, Paolo Vicini
Author Information
  1. Marilee A Andrew: Applied Physics Laboratory and the Department of Bioengineering at the University of Washington, Seattle, WA 98105-6698, USA. marilee@apl.washington.edu

Abstract

Disposition of drugs in pregnant women is poorly understood in spite of widespread prescription of drugs to women during gestation. We have developed a whole body physiologically based pharmacokinetic (PBPK) model to explore the effects of pregnancy on pharmacokinetics. The model accounts for maternofetal changes over the course of gestation; physiological and drug-specific parameters are taken from literature. Here we preliminarily demonstrate the model's utility to predict midazolam pharmacokinetics following intravenous bolus dosing in women undergoing Caesarian section. Simulations of maternal venous plasma concentrations compare favorably with data extracted from historical studies.

Grants

  1. P41 EB001975/NIBIB NIH HHS
  2. U10 HD047892/NICHD NIH HHS

MeSH Term

Anti-Anxiety Agents
Computer Simulation
Female
Fetus
Humans
Maternal-Fetal Exchange
Metabolic Clearance Rate
Midazolam
Models, Biological
Organ Specificity
Pregnancy
Tissue Distribution

Chemicals

Anti-Anxiety Agents
Midazolam

Word Cloud

Created with Highcharts 10.0.0womenmodeldrugsgestationbasedpharmacokineticpregnancypharmacokineticsmidazolamDispositionpregnantpoorlyunderstoodspitewidespreadprescriptiondevelopedwholebodyphysiologicallyPBPKexploreeffectsaccountsmaternofetalchangescoursephysiologicaldrug-specificparameterstakenliteraturepreliminarilydemonstratemodel'sutilitypredictfollowingintravenousbolusdosingundergoingCaesariansectionSimulationsmaternalvenousplasmaconcentrationscomparefavorablydataextractedhistoricalstudiesPhysiologicallydisposition

Similar Articles

Cited By