Validation of a Limited Sampling Model to Determine Etoposide Area Under the Curve |
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| Authors: | Bert L. Lum Pharm.D. Kevin J. Lane Pharm.D. Timothy W. Synold Pharm.D. Adrian Goram Pharm.D. Steven B. Charnick Ph.D. Branimir I. Sikic M.D. |
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| Affiliation: | 1. From the Divisions of Oncology and Clinical Pharmacology, Stanford University School of Medicine, Stanford, California (Drs. Lum and Sikic);2. the Pharmacy Service Education and Research Center, Palo Alto Veterans Administration Health Care System, Palo Alto, California (Drs. Lum and Lane);3. the University of Pacific School of Pharmacy, Stockton, California (Dr. Lum);4. the University of Southern California, Los Angeles, California (Dr. Lum);5. the Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, California (Dr. Synold);6. the School of Pharmacy, Virginia Commonwealth University, Medical College of Virginia, Richmond, Virginia (Dr. Goram);7. and the Department of Clinical Pharmacology, Sandoz Research Institute, East Hanover, New Jersey (Dr. Charnick). |
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| Abstract: | ![]()
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<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∞ 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. (Pharmacotherapy 1997;17(5):887–890) |
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