Population Pharmacokinetic Parameters of Gentamicin in Patients With Solid Tumors: Estimation by One- and Two-Stage Methods

Abstract

Gentamicin monitoring has been improved with the introduction of Bayesian methods but the usefulness depends on the quality of the population parameters (PP) used. The objective of this study was to determine PP of gentamicin in patients with solid tumors. A total of 198 adult patients with cancer were included in the analysis. Population parameters were estimated by both a two-stage and a one-stage method (NPEM, Non Parametric Expectation Maximization). Individual parameters (IP) were estimated by the Sawchuk-Zaske method and by nonlinear regression. The estimated distribution volume and clearance of gentamicin (mean +/- SD) were 18.37 +/- 5.021 (0.30-0.32 l/kg of dosing weight) and 3.34 +/- 1.6 l/h, respectively. No significant differences between IP or PP obtained by the different methods were found. The results indicated a wide variability of gentamicin pharmacokinetics making monitoring necessary and that patients with solid tumors may have larger gentamicin volume and slower clearance than normal patients. These observations imply that different population pharmacokinetic parameters should be used for this group of patients.