Physiologically based pharmacokinetic model of midazolam disposition during pregnancy.
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.
Andrew
Marilee A
MA
Applied Physics Laboratory and the Department of Bioengineering at the University of Washington, Seattle, WA 98105-6698, USA. marilee@apl.washington.edu
Hebert
Mary F
MF
Vicini
Paolo
P
D014151:Anti-Anxiety Agents / Q000097:blood / Q000493:pharmacokinetics; D003198:Computer Simulation; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000097:blood* / Q000493:pharmacokinetics*; D008954:Models, Biological; D009928:Organ Specificity; D011247:Pregnancy / Q000378:metabolism*; D014018:Tissue Distribution
D014151:Anti-Anxiety Agents; D008874:Midazolam