Validation of a Limited Sampling Model to Determine Etoposide Area Under the Curve

Study Objective. To validate the utility of a previously reported 3-point limited sampling model (LSM) for determining etoposide area under the curve to infinity (AUC∞). Design. Secondary analysis of data from two clinical trials of etoposide. Setting. University medical center clinical research center. Patients. Thirty-four patients with different malignancies. Interventions. Etoposide was administered as a 2-hour infusion to 34 patients. Serial plasma samples were drawn over 24 hours after the infusion and analyzed for etoposide by high-performance liquid chromatography. Measurements and Main Results. The 3-point LSM AUC was compared with a 14-point actual AUC calculated by the linear trapezoidal rule. Actual and predicted AUC∞ by the LSM were highly correlated (r=0.97, p 12%) tended to have abnormally low or high peak concentrations. Conclusion. Our findings suggest the development of more robust LSM using other techniques, such as pharmacostatistical models, that can accommodate a greater degree of pharmacokinetic variability.