RESUMO
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(infinity)). 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(infinity) by the LSM were highly correlated (r=0.97, p<0.0001). The LSM predictions had a mean absolute error of 10.9% (95% CI -14.1, -5.3) and a mean error of -9.7% (95% CI 6.9, 14.9). Nine patients with poor AUC(infinity) estimations by the LSM (error > 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.
