Lithium Population Pharmacokinetics from Routine Clinical Data

Abstract

Routine clinical pharmacokinetic data (n = 303) collected from 90 patients receiving lithium have been analyzed to evaluate the role of patient characteristics for estimating dosing regimens. The data were analyzed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The pharmacokinetic model of lithium was described using a one-compartment steady-state model. The effect of a variety of developmental and demographic factors on clearance was investigated. NONMEM estimates indicated that lithium clearance was influenced by the demographic variables of age, total body weight, and serum creatinine. The interindividual variability in lithium clearance was modeled with proportional error with an estimated coefficient of variation of 25.1%. The intraindividual variability, or residual error, was 14.3%. The dosing method based on clearance values obtained by NONMEM analysis allowed the prediction of the minimum steady-state lithium concentration as a function of maintenance dose with acceptable error for therapeutic drug monitoring.