Population Pharmacokinetics of Lithium Carbonate in Young Male Healthy Chinese Volunteers

Yu, Weifeng; Sun, Xue; Li, Y; Li, M; Wang, K; Li, H

doi:10.1055/s-0042-103329

Cited by 9 publications

(4 citation statements)

References 9 publications

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“…This is expected given the sparse blood samples in our dataset. The estimated CL/F from the final model was 1.43 L/hr, which lies within the range of those reported from previous studies (0.41 to 9.39 L/hr; ElDesoky, Kumar, Alorainy, Hamdi, & Derendorf, ; Findling et al, ; Jermain et al, ; Landersdorfer, Findling, Frazier, Kafantaris, & Kirkpatrick, ; Mason, McQueen, Keary, & James, ; Methaneethorn, ; Perez‐Castello et al, ; Türck, Heinzel, & Luik, ; Yu et al, ; Yukawa, Nomiyama, Higuchi, & Aoyama, ). Generally, lithium clearance is approximately 20% of creatinine clearance (Bauer, ).…”

Section: Discussionsupporting

confidence: 85%

Factors influencing lithium pharmacokinetics in patients with acute mania: A population pharmacokinetic analysis

Methaneethorn

Sringam

2019

Human Psychopharmacology

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Objective: The objective of this study was to conduct a population pharmacokinetic model of lithium in Thai patients with acute mania.Methods: Lithium concentrations from 222 acute manic patients were included in this study. The population pharmacokinetic model was developed using NONMEM 7.3 software. Influences of potential covariates including body size, age, renal function, and gender were evaluated through a stepwise approach. Bootstrap analysis and an external validation approach were used to evaluate the robustness and predictability of the final model. Results:A one-compartment model adequately described lithium pharmacokinetics.Body weight and age were significant predictors for lithium clearance, with the following relationship: CL/F (L/hr) = 1.43 * (WT/65) 0.425 * (age/38) −0.242 . The population estimates of lithium clearance, volume of distribution, and absorption rate constant of the final model were 1.43 L/hr, 54 L (fixed), and 0.426 hr −1 (fixed), respectively.Model evaluation showed that the final model was predictive and robust.Conclusions: A population pharmacokinetic model of lithium with good performance was developed in Thai patients with acute mania. This model can be used to assist clinicians in individualized lithium therapy.

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Section: Discussionsupporting

confidence: 85%

Factors influencing lithium pharmacokinetics in patients with acute mania: A population pharmacokinetic analysis

Methaneethorn

Sringam

2019

Human Psychopharmacology

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“…The elimination half-life of lithium averages approximately 20–24 hrs, and steady-state concentrationsare reached after 5–7 days 6,18. Therefore, the steady-state blood lithium concentration was measured after administration of oral lithium carbonate 1.0 g/d for 1 week.…”

Section: Methodsmentioning

confidence: 99%

<p>Factors related to lithium blood concentrations in Chinese Han patients with bipolar disorder</p>

Xu¹,

Xia

Liang³

et al. 2019

NDT

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Background: The goal of this study was to identify the physiological factors related to the blood concentration of lithium in Chinese Han patients with bipolar disorder (BD). Materials and methods: A total of 186 Chinese Han patients with BD were assessed. Patients were recruited from the Anhui Mental Health Center. The concentrations of serum lithium were measured by a Dimension RxL Max biochemistry analyzer. Physiological factors, including body weight, body mass index (BMI), and routine laboratory parameters, were collected. Relationships between the serum lithium concentration and relevant clinical data were analyzed by Pearson correlation tests, and the independent relationships were determined by multivariate linear regression analysis. Results: Pearson correlation analysis showed that serum lithium concentrations were positively correlated with creatinine concentrations (r=0.147, P =0.046), Mg 2+ concentrations (r=0.151, P =0.04), and the percentage of neutrophils (r=0.178, P =0.015) and negatively correlated with high-density lipoprotein (HDL) concentrations (r=−0.142, P =0.05), apolipoprotein A1 concentrations (r=−0.169, P =0.02), and Na + concentrations (r=−0.148, P =0.046) in 186 patients with BD. Furthermore, multivariate linear regression analysis showed that serum lithium concentrations were negatively associated with Na + concentrations and positively associated with the percentage of neutrophils. Conclusion: These results suggest that physiological factors, including creatinine, HDL, apolipoprotein A1, Na + , and Mg 2+ concentrations and percentage of neutrophils, might be related to serum lithium concentrations and provide a basis for parameter selection of lithium population pharmacokinetics in Chinese Han patients with BD.

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“…The inclusion of body weight as an allometric factor significantly improved the model fit, while age and sex were not associated with PKs of lithium. Yu et al studied lithium carbonate PPK in 20 healthy young male Chinese volunteers; no covariate was retained in the final model because of the narrow distribution of demographic and biological variables ( Yu et al, 2016 ). This limits the usefulness of this model in predicting the PK of lithium carbonate in the elderly.…”

Section: Introductionmentioning

confidence: 99%

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

Jin

Cui

et al. 2022

Front. Pharmacol.

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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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Population Pharmacokinetics of Lithium Carbonate in Young Male Healthy Chinese Volunteers

Cited by 9 publications

References 9 publications

Factors influencing lithium pharmacokinetics in patients with acute mania: A population pharmacokinetic analysis

Factors influencing lithium pharmacokinetics in patients with acute mania: A population pharmacokinetic analysis

<p>Factors related to lithium blood concentrations in Chinese Han patients with bipolar disorder</p>

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

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