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

Horton S, Tuerk A, Cook D, Cook J, Dhurjati P - Adv Bioinformatics (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Colburn Laboratory, Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Terminal concentration profiles in selected physiological compartments for dosage regimens that are known to cause birth defects. In this case, lithium medication is administered twice daily and controlled-release tablets release lithium over 4 hours. A pulse function corresponding to the drug absorption is shown above each figure. (a) One dose of a 450 mg tablet (12 mEq lithium) with a subsequent 900 mg (24 mEq lithium) dose. (b) Two doses of a 900 mg tablet (24 mEq lithium).
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fig3: Terminal concentration profiles in selected physiological compartments for dosage regimens that are known to cause birth defects. In this case, lithium medication is administered twice daily and controlled-release tablets release lithium over 4 hours. A pulse function corresponding to the drug absorption is shown above each figure. (a) One dose of a 450 mg tablet (12 mEq lithium) with a subsequent 900 mg (24 mEq lithium) dose. (b) Two doses of a 900 mg tablet (24 mEq lithium).

Mentions: Lithium is known to cause birth defects in infants; although there have been no clinical trials to ascertain the exact dosage that causes harm. There are, however, several reported cases of women who continued to take lithium during their pregnancy, gave birth to a baby with birth defects, and the doctors reported the dosage regimen. One-dosage regimen that has been documented to cause birth defects was two capsules daily, 450 mg in the morning followed by 900 mg in the evening [2]. There are numerous sources, including the International Register of Lithium Babies, that document birth defects as a result of treatment with lithium. However, the dosage regimens used are not reported or accessible. The standard dosage of two 900 mg doses daily was used to describe the dosage profiles for these cases. The predicted lithium concentrations over time associated with these dosing regimens are shown in Figure 3 for the brain, plasma, fetus, and the uterus.


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

Horton S, Tuerk A, Cook D, Cook J, Dhurjati P - Adv Bioinformatics (2012)

Terminal concentration profiles in selected physiological compartments for dosage regimens that are known to cause birth defects. In this case, lithium medication is administered twice daily and controlled-release tablets release lithium over 4 hours. A pulse function corresponding to the drug absorption is shown above each figure. (a) One dose of a 450 mg tablet (12 mEq lithium) with a subsequent 900 mg (24 mEq lithium) dose. (b) Two doses of a 900 mg tablet (24 mEq lithium).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369391&req=5

fig3: Terminal concentration profiles in selected physiological compartments for dosage regimens that are known to cause birth defects. In this case, lithium medication is administered twice daily and controlled-release tablets release lithium over 4 hours. A pulse function corresponding to the drug absorption is shown above each figure. (a) One dose of a 450 mg tablet (12 mEq lithium) with a subsequent 900 mg (24 mEq lithium) dose. (b) Two doses of a 900 mg tablet (24 mEq lithium).
Mentions: Lithium is known to cause birth defects in infants; although there have been no clinical trials to ascertain the exact dosage that causes harm. There are, however, several reported cases of women who continued to take lithium during their pregnancy, gave birth to a baby with birth defects, and the doctors reported the dosage regimen. One-dosage regimen that has been documented to cause birth defects was two capsules daily, 450 mg in the morning followed by 900 mg in the evening [2]. There are numerous sources, including the International Register of Lithium Babies, that document birth defects as a result of treatment with lithium. However, the dosage regimens used are not reported or accessible. The standard dosage of two 900 mg doses daily was used to describe the dosage profiles for these cases. The predicted lithium concentrations over time associated with these dosing regimens are shown in Figure 3 for the brain, plasma, fetus, and the uterus.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Colburn Laboratory, Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus