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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

Model-predicted pathological dosage regimens. The maximum and average fetus concentrations from the 450/900 dosage regimen are plotted along with two new dosage regimens. A 300/1000 dosage regimen is shown in black and a 700/700 dosage regimen is shown in blue.
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fig4: Model-predicted pathological dosage regimens. The maximum and average fetus concentrations from the 450/900 dosage regimen are plotted along with two new dosage regimens. A 300/1000 dosage regimen is shown in black and a 700/700 dosage regimen is shown in blue.

Mentions: The previously documented pathological cases are primarily useful in ruling out other potential dosage regimens. To this end, we selected two dosing regimens within the therapeutic dose range where the effect on the fetus is unknown. The first dosage regimen we modeled is two 700 mg doses, 12 hrs apart (denoted 700/700). The next dosage regimen is a 1000 mg dose followed by a 300 mg dose 12 hrs later. The results of these simulations are shown in Figure 4.


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)

Model-predicted pathological dosage regimens. The maximum and average fetus concentrations from the 450/900 dosage regimen are plotted along with two new dosage regimens. A 300/1000 dosage regimen is shown in black and a 700/700 dosage regimen is shown in blue.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Model-predicted pathological dosage regimens. The maximum and average fetus concentrations from the 450/900 dosage regimen are plotted along with two new dosage regimens. A 300/1000 dosage regimen is shown in black and a 700/700 dosage regimen is shown in blue.
Mentions: The previously documented pathological cases are primarily useful in ruling out other potential dosage regimens. To this end, we selected two dosing regimens within the therapeutic dose range where the effect on the fetus is unknown. The first dosage regimen we modeled is two 700 mg doses, 12 hrs apart (denoted 700/700). The next dosage regimen is a 1000 mg dose followed by a 300 mg dose 12 hrs later. The results of these simulations are shown in Figure 4.

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