Calculation of Lithium Clearance for Clinical use Based on Renal Excretion in Japanese Patients

Background: It is recommended to adjust the dosage of lithium carbonate, primarily used in the treatment of mania, based on the serum lithium concentration at steady-state (Css). It has been suggested that factors associated with renal function should be included in the estimation of lithium clearance (Li-CL) due to its elimination via renal excretion. In the present study, parameters affecting Li-CL were investigated in Japanese patients. Methods: Retrospective analysis was performed in patients who had chronically received lithium carbonate, by stepwise regression analysis, with Li-CL as the dependent variable and gender, age, weight and creatinine clearance (Ccr) as independent variables. Ccr was calculated using the Cockcroft-Gault equation, and Li-CL was calculated as the reciprocal value of Css per daily dose. Results: Seventy-two patients were enrolled in this study. Regression analysis revealed that only Ccr was an independent variable (P<0.001), and the following equation was obtained: Li-CL (mL/min) = 0.161 × Ccr (mL/min) + 6.47. This equation was then validated by comparison with previously reported methods using a separate population of patients. The bias and precision of the equation’s predictions were evaluated by calculating the mean prediction error, mean absolute error and root mean squared prediction error. Although the Jermain method had the least bias, no significant differences were observed between the present and Jermain methods. Conclusion: Because the equation of the present study includes Ccr as a parameter of renal function, this may better provide appropriate dosing and safety of lithium therapy in Japanese patients.