Population Pharmacokinetics of Lithium Carbonate in Young Male Healthy Chinese Volunteers

W. Yu; X. Sun; Y. Li; M. Li; K. Wang; H. Li

doi:10.1055/s-0042-103329

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2016; 49(05): 177-181
DOI: 10.1055/s-0042-103329

Original Paper

Population Pharmacokinetics of Lithium Carbonate in Young Male Healthy Chinese Volunteers

Authors

W. Yu^*

¹Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
X. Sun^*

¹Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Y. Li

¹Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
M. Li

²Department of Pharmacometrics, Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
K. Wang

²Department of Pharmacometrics, Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
H. Li

¹Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Abstract

Aim: To investigate the population pharmacokinetics (PK) model of lithium carbonate in young male healthy Chinese subjects.

Methods: This study was conducted using a 2-period crossover design. 20 healthy male subjects received lithium carbonate tablets from 2 different Chinese pharmaceutical manufacturers. Plasma samples were obtained by blood sampling over 72 h in each period. Population PK analysis was performed using nonlinear mixed-effects model (NONMEM) software. The final models were validated using bootstrap and visual predictive check (VPC) approaches.

Results: The final PK model was a two-compartment model. The population PK parameters, clearance (CL/F), apparent distribution volume of the central compartment (V2/F), inter-compartmental clearance (Q/F) and apparent distribution volume of the peripheral compartment (V3/F), were 9.39 L/h, 10.4 L, 22.1 L/h, and 216 L, respectively.

Conclusion: Population PK models for lithium carbonate have been developed and considerable inter-subject variability was found in healthy young male Chinese subjects. It takes a long time to achieve the steady state in conventional therapy. This may provide guidelines for future use of lithium carbonate in China.

Key words

lithium - healthy young male chinese subjects - population pharmacokinetics

Full Text

References

References
1 Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. J Lancet 2013; 381: 1672-1682
2 Grandjean EM, Aubry JM. Lithium: updated human knowledge using an evidence-based approach: Part I: Clinical efficacy in bipolar disorder. J CNS Drugs 2009; 23: 225-240
3 Osher Y, Bersudsky Y, Belmaker RH. The New Lithium Clinic. J Neuropsychobiology 2010; 62: 17-26
4 Prevention and treatment of mental disorders of Chinese Guide – bipolar disorder guide, published in 2006
5 Dyson EH, Simpson D, Prescott LF et al. Self-poisoning and therapeutic intoxication with lithium. J Hum Toxicol 1987; 6: 325-329
6 Lee YC, Lin JL, Lee SY et al. Outcome of patients with lithium poisoning at a far-east poison center.. J Hum Exp Toxicol 2011; 30: 528-534
7 Waring WS, Laing WJ, Good AM et al. Pattern of lithium exposure predicts poisoning severity: evaluation of referrals to a regional poisons unit. J QJM 2007; 100: 271-276
8 Mcknight RF, Adida M, Budge K et al. Lithium toxicity profile: a systematic review and meta-analysis. J Lancet 2012; 379: 721-728
9 Bergstrand M, Hooker AC, Wallin JE et al. Prediction corrected visual predictive checks for diagnosing nonlinear mixed-effects models. J AAPS 2011; 13: 143-151
10 Guilherme MC, Pereira DG, Galuppo MP et al. Bioequivalence of two lithium formulations in healthy volunteers. J Arzneimittelforschung 2006; 56: 524-528
11 Lee CF, Yang YY, Hu OY. Single dose pharmacokinetic study of lithium in Taiwanese/Chinese bipolar patients. J Aust N Z J Psychiatry 1998; 32: 133-136