{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:57:29Z","timestamp":1778875049710,"version":"3.51.4"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T00:00:00Z","timestamp":1656892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background<\/jats:bold>: 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.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>: 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.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>: Lithium PK was described by a one-compartment model with first-order absorption and elimination processes. The typical estimated apparent clearance was 0.909\u00a0L\/h<jats:sup>\u22121<\/jats:sup> with 16.4% between-subject variability in the 62\u00a0kg patients with 116\u00a0ml\/min creatinine clearance and 600\u00a0mg daily doses. To achieve a target trough concentration (0.4\u20130.8\u00a0mmol\/L) in the maintenance phase, the regimen of 500\u00a0mg than 750\u00a0mg daily dose was recommended for patients with renal insufficiency and weighing 100\u00a0kg.<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>: 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\u2019s clearance. These results demonstrate the nonlinear renal excretion of lithium; hence, dosage adjustments are recommended for patients with renal insufficiency.<\/jats:p>","DOI":"10.3389\/fphar.2022.913935","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T04:34:52Z","timestamp":1656909292000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder"],"prefix":"10.3389","volume":"13","author":[{"given":"Zi-bin","family":"Jin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-fan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue-peng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-bo","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-yong","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s10928-019-09635-6","article-title":"Operating Characteristics of Stepwise Covariate Selection in Pharmacometric Modeling","volume":"46","author":"Ahamadi","year":"2019","journal-title":"J. Pharmacokinet. Pharmacodyn."},{"key":"B2","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1097\/YIC.0000000000000301","article-title":"Estimation of Lithium Clearance in Patients with Bipolar Disorder","volume":"35","author":"Alqahtani","year":"2020","journal-title":"Int. Clin. Psychopharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e51","DOI":"10.1038\/psp.2013.26","article-title":"Establishing Best Practices and Guidance in Population Modeling: an Experience with an Internal Population Pharmacokinetic Analysis Guidance","volume":"2","author":"Byon","year":"2013","journal-title":"CPT Pharmacometrics Syst. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1093\/biomet\/asr023","article-title":"Conditional Akaike Information under Generalized Linear and Proportional Hazards Mixed Models","volume":"98","author":"Donohue","year":"2011","journal-title":"Biometrika"},{"key":"B5","doi-asserted-by":"publisher","first-page":"617","DOI":"10.5414\/cpp46617","article-title":"Estimation of Lithium Clearance from Routine Clinical Data in Egyptian Bipolar Patients. A Population Pharmacokinetic Approach","volume":"46","author":"ElDesoky","year":"2008","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1177\/0091270003253624","article-title":"Model Appropriateness and Population Pharmacokinetic Modeling","volume":"43","author":"Ette","year":"2003","journal-title":"J. Clin. Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1097\/JCP.0b013e3181e66a62","article-title":"First-dose Pharmacokinetics of Lithium Carbonate in Children and Adolescents","volume":"30","author":"Findling","year":"2010","journal-title":"J. Clin. Psychopharmacol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"331","DOI":"10.2165\/00023210-200923040-00005","article-title":"Lithium: Updated Human Knowledge Using an Evidence-Based Approach. Part II: Clinical Pharmacology and Therapeutic Monitoring","volume":"23","author":"Grandjean","year":"2009","journal-title":"CNS drugs"},{"key":"B9","doi-asserted-by":"publisher","first-page":"376","DOI":"10.3389\/fphar.2021.650298","article-title":"Population Pharmacokinetics of Lithium","volume":"10","author":"Jermain","year":"1991","journal-title":"Clin. Pharm."},{"key":"B10","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s40262-016-0430-3","article-title":"Lithium in Paediatric Patients with Bipolar Disorder: Implications for Selection of Dosage Regimens via Population Pharmacokinetics\/pharmacodynamics","volume":"56","author":"Landersdorfer","year":"2017","journal-title":"Clin. Pharmacokinet."},{"key":"B12","year":"2020"},{"key":"B13","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.jad.2017.03.052","article-title":"The Use of Lithium for the Treatment of Bipolar Disorder: Recommendations from Clinical Practice Guidelines","volume":"217","author":"Malhi","year":"2017","journal-title":"J. Affect Disord."},{"key":"B14","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/BF01061469","article-title":"Building Population Pharmacokinetic-Ppharmacodynamic Models. I. Models for Covariate Effects","volume":"20","author":"Mandema","year":"1992","journal-title":"J. Pharmacokinet. Biopharm."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e2697","DOI":"10.1002\/hup.2697","article-title":"Factors Influencing Lithium Pharmacokinetics in Patients with Acute Mania: A Population Pharmacokinetic Analysis","volume":"34","author":"Methaneethorn","year":"2019","journal-title":"Hum. Psychopharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1868","DOI":"10.1016\/j.euroneuro.2016.11.005","article-title":"Population Pharmacokinetic Model of Lithium and Drug Compliance Assessment","volume":"26","author":"P\u00e9rez-Castell\u00f3","year":"2016","journal-title":"Eur. Neuropsychopharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1056\/NEJM199409013310907","article-title":"Lithium in the Treatment of Mood Disorders","volume":"331","author":"Price","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1111\/j.1399-5618.2007.00475.x","article-title":"What Is the Optimal Serum Lithium Level in the Long-Term Treatment of Bipolar Disorder-Aa Review?","volume":"10","author":"Severus","year":"2008","journal-title":"Bipolar Disord."},{"key":"B19","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1002\/bdd.2116","article-title":"Nonlinear Disposition of Lithium in Rats and Saturation of its Tubular Reabsorption by the Sodium-Phosphate Cotransporter as a Cause","volume":"39","author":"Uwai","year":"2018","journal-title":"Biopharm. Drug Dispos."},{"key":"B20","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1002\/j.1552-4604.1994.tb01994.x","article-title":"Clinical Pharmacokinetics of Lithium","volume":"34","author":"Ward","year":"1994","journal-title":"J. Clin. Pharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1097\/00004714-199706000-00007","article-title":"Lithium Pharmacokinetics in Chinese Manic-Depressive Patients","volume":"17","author":"Wing","year":"1997","journal-title":"J. Clin. Psychopharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/bdi.12609","article-title":"Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 Guidelines for the Management of Patients with Bipolar Disorder","volume":"20","author":"Yatham","year":"2018","journal-title":"Bipolar Disord."},{"key":"B23","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1055\/s-0042-103329","article-title":"Population Pharmacokinetics of Lithium Carbonate in Young Male Healthy Chinese Volunteers","volume":"49","author":"Yu","year":"2016","journal-title":"Pharmacopsychiatry"},{"key":"B24","doi-asserted-by":"publisher","first-page":"650298","DOI":"10.3389\/fphar.2021.650298","article-title":"Population Pharmacokinetics of Lithium in Young Pediatric Patients with Intellectual Disability","volume":"12","author":"Yuan","year":"2021","journal-title":"Front. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.913935\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T04:34:55Z","timestamp":1656909295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.913935\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,4]]},"references-count":23,"alternative-id":["10.3389\/fphar.2022.913935"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.913935","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,4]]},"article-number":"913935"}}