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)).Secondary analysis of data from two clinical trials of etoposide.University medical center clinical research center.Thirty-four patients with different malignancies.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.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.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.
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View details for PubMedID 9324178