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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.913935/full |
| _version_ | 1828336001441857536 |
|---|---|
| author | Zi-bin Jin Zhuo Wu Yi-fan Cui Yi-fan Cui Xue-peng Liu Hong-bo Liang Jia-yong You Chen-yu Wang |
| author_facet | Zi-bin Jin Zhuo Wu Yi-fan Cui Yi-fan Cui Xue-peng Liu Hong-bo Liang Jia-yong You Chen-yu Wang |
| author_sort | Zi-bin Jin |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T21:54:50Z |
| format | Article |
| id | doaj.art-a65b4c792bab413fa079bfa70c3ec943 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T21:54:50Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-a65b4c792bab413fa079bfa70c3ec9432022-12-22T02:28:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.913935913935Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar DisorderZi-bin Jin0Zhuo Wu1Yi-fan Cui2Yi-fan Cui3Xue-peng Liu4Hong-bo Liang5Jia-yong You6Chen-yu Wang7Department of Medical Psychology, The Affiliated Xuzhou Eastern Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Pharmacy, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaDepartment of Medical Psychology, The Affiliated Xuzhou Eastern Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Medical Psychology, The Affiliated Xuzhou Eastern Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Medical Service, Xuzhou Civil Affairs Psychiatric Hospital, Xuzhou, ChinaDepartment of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.913935/fulllithiumbipolar disorderpopulation pharmacokineticsMonte Carlo simulationdosage regimen |
| spellingShingle | Zi-bin Jin Zhuo Wu Yi-fan Cui Yi-fan Cui Xue-peng Liu Hong-bo Liang Jia-yong You Chen-yu Wang Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder Frontiers in Pharmacology lithium bipolar disorder population pharmacokinetics Monte Carlo simulation dosage regimen |
| 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 | lithium bipolar disorder population pharmacokinetics Monte Carlo simulation dosage regimen |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.913935/full |
| work_keys_str_mv | AT zibinjin populationpharmacokineticsanddosingregimenoflithiuminchinesepatientswithbipolardisorder AT zhuowu populationpharmacokineticsanddosingregimenoflithiuminchinesepatientswithbipolardisorder AT yifancui populationpharmacokineticsanddosingregimenoflithiuminchinesepatientswithbipolardisorder AT yifancui populationpharmacokineticsanddosingregimenoflithiuminchinesepatientswithbipolardisorder AT xuepengliu populationpharmacokineticsanddosingregimenoflithiuminchinesepatientswithbipolardisorder AT hongboliang populationpharmacokineticsanddosingregimenoflithiuminchinesepatientswithbipolardisorder AT jiayongyou populationpharmacokineticsanddosingregimenoflithiuminchinesepatientswithbipolardisorder AT chenyuwang populationpharmacokineticsanddosingregimenoflithiuminchinesepatientswithbipolardisorder |