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Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder

Background: Lithium is an effective medication approved for the treatment of bipolar disorder (BD). It has a narrow therapeutic index (TI) and requires therapeutic drug monitoring. This study aimed to conduct a population pharmacokinetics (PPK) analysis of lithium and investigate the appropriateness...

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Autores principales: Jin, Zi-bin, Wu, Zhuo, Cui, Yi-fan, Liu, Xue-peng, Liang, Hong-bo, You, Jia-yong, Wang, Chen-yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289112/
https://www.ncbi.nlm.nih.gov/pubmed/35860024
http://dx.doi.org/10.3389/fphar.2022.913935
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author Jin, Zi-bin
Wu, Zhuo
Cui, Yi-fan
Liu, Xue-peng
Liang, Hong-bo
You, Jia-yong
Wang, Chen-yu
author_facet Jin, Zi-bin
Wu, Zhuo
Cui, Yi-fan
Liu, Xue-peng
Liang, Hong-bo
You, Jia-yong
Wang, Chen-yu
author_sort Jin, Zi-bin
collection PubMed
description Background: Lithium is an effective medication approved for the treatment of bipolar disorder (BD). It has a narrow therapeutic index (TI) and requires therapeutic drug monitoring. This study aimed to conduct a population pharmacokinetics (PPK) analysis of lithium and investigate the appropriateness of the dosing regimen according to different patient characteristics. Methods: A total of 476 lithium concentrations from 268 patients with bipolar disorder were analyzed using nonlinear mixed-effects modeling. Monte Carlo simulations were employed to investigate the influence of covariates, such as weight, creatinine clearance, and daily doses of lithium concentrations, and to determine the individualized dosing regimens for patients. Results: Lithium PK was described by a one-compartment model with first-order absorption and elimination processes. The typical estimated apparent clearance was 0.909 L/h(−1) with 16.4% between-subject variability in the 62 kg patients with 116 ml/min creatinine clearance and 600 mg daily doses. To achieve a target trough concentration (0.4–0.8 mmol/L) in the maintenance phase, the regimen of 500 mg than 750 mg daily dose was recommended for patients with renal insufficiency and weighing 100 kg. Conclusion: A PPK model for lithium was developed to determine the influence of patient characteristics on lithium pharmacokinetics. Weight, creatinine clearance, and total daily dose of lithium can affect the drug’s clearance. These results demonstrate the nonlinear renal excretion of lithium; hence, dosage adjustments are recommended for patients with renal insufficiency.
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spelling pubmed-92891122022-07-19 Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder Jin, Zi-bin Wu, Zhuo Cui, Yi-fan Liu, Xue-peng Liang, Hong-bo You, Jia-yong Wang, Chen-yu Front Pharmacol Pharmacology Background: Lithium is an effective medication approved for the treatment of bipolar disorder (BD). It has a narrow therapeutic index (TI) and requires therapeutic drug monitoring. This study aimed to conduct a population pharmacokinetics (PPK) analysis of lithium and investigate the appropriateness of the dosing regimen according to different patient characteristics. Methods: A total of 476 lithium concentrations from 268 patients with bipolar disorder were analyzed using nonlinear mixed-effects modeling. Monte Carlo simulations were employed to investigate the influence of covariates, such as weight, creatinine clearance, and daily doses of lithium concentrations, and to determine the individualized dosing regimens for patients. Results: Lithium PK was described by a one-compartment model with first-order absorption and elimination processes. The typical estimated apparent clearance was 0.909 L/h(−1) with 16.4% between-subject variability in the 62 kg patients with 116 ml/min creatinine clearance and 600 mg daily doses. To achieve a target trough concentration (0.4–0.8 mmol/L) in the maintenance phase, the regimen of 500 mg than 750 mg daily dose was recommended for patients with renal insufficiency and weighing 100 kg. Conclusion: A PPK model for lithium was developed to determine the influence of patient characteristics on lithium pharmacokinetics. Weight, creatinine clearance, and total daily dose of lithium can affect the drug’s clearance. These results demonstrate the nonlinear renal excretion of lithium; hence, dosage adjustments are recommended for patients with renal insufficiency. Frontiers Media S.A. 2022-07-04 /pmc/articles/PMC9289112/ /pubmed/35860024 http://dx.doi.org/10.3389/fphar.2022.913935 Text en Copyright © 2022 Jin, Wu, Cui, Liu, Liang, You and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Jin, Zi-bin
Wu, Zhuo
Cui, Yi-fan
Liu, Xue-peng
Liang, Hong-bo
You, Jia-yong
Wang, Chen-yu
Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder
title Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder
title_full Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder
title_fullStr Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder
title_full_unstemmed Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder
title_short Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder
title_sort population pharmacokinetics and dosing regimen of lithium in chinese patients with bipolar disorder
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289112/
https://www.ncbi.nlm.nih.gov/pubmed/35860024
http://dx.doi.org/10.3389/fphar.2022.913935
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