Estimation of lithium clearance in patients with bipolar disorder

Abstract

Lithium is an effective agent approved for the treatment of bipolar disorder. It has narrow therapeutic window and significant variability in its pharmacokinetic. The aim of this study is to determine the population pharmacokinetics of lithium in patients with bipolar disorder in Saudi Arabia and to identify the factors that explain variability. A retrospective chart review was performed on patients with bipolar disorder who received oral lithium. The population pharmacokinetic models were developed using Monolix 4.4. After the appropriate base model was established, five covariates were tested, namely age, sex, weight, serum creatinine, and creatinine clearance. The analysis included a total of 170 lithium plasma concentrations from 31 patients. The data were adequately described by a two-compartment open model with linear absorption and elimination. The average parameter estimates for lithium CL/F, V1/F, V2/F, and Q/F were estimated. The inter-individual variability (coefficients of variation) in CL was 42%. The most significant covariate on lithium CL was found to be creatinine clearance. The population pharmacokinetic model of lithium in patients with bipolar disorder in Saudi Arabia was established. Our findings showed that creatinine clearance is the most significant covariate on lithium clearance. Further studies are required to understand the factors that may influence the pharmacokinetics of lithium and assist in drug dosage decisions.