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Advances in Bioinformatics
Volume 2012 (2012), Article ID 352729, 9 pages
Research Article

Maximum Recommended Dosage of Lithium for Pregnant Women Based on a PBPK Model for Lithium Absorption

1Colburn Laboratory, Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA
2Resident in the Department of Family Medicine, Christiana Care Health Services, Wilmington, DE 19805, USA

Received 26 December 2011; Revised 10 February 2012; Accepted 13 February 2012

Academic Editor: Huixiao Hong

Copyright © 2012 Scott Horton et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Treatment of bipolar disorder with lithium therapy during pregnancy is a medical challenge. Bipolar disorder is more prevalent in women and its onset is often concurrent with peak reproductive age. Treatment typically involves administration of the element lithium, which has been classified as a class D drug (legal to use during pregnancy, but may cause birth defects) and is one of only thirty known teratogenic drugs. There is no clear recommendation in the literature on the maximum acceptable dosage regimen for pregnant, bipolar women. We recommend a maximum dosage regimen based on a physiologically based pharmacokinetic (PBPK) model. The model simulates the concentration of lithium in the organs and tissues of a pregnant woman and her fetus. First, we modeled time-dependent lithium concentration profiles resulting from lithium therapy known to have caused birth defects. Next, we identified maximum and average fetal lithium concentrations during treatment. Then, we developed a lithium therapy regimen to maximize the concentration of lithium in the mother’s brain, while maintaining the fetal concentration low enough to reduce the risk of birth defects. This maximum dosage regimen suggested by the model was 400 mg lithium three times per day.