Article

Limited sampling models for reliable estimation of etoposide area under the curve

Klinische Nuklearmedizin, Philipps-Universität Marburg, Germany.
European Journal of Cancer (Impact Factor: 5.42). 11/1995; 31A(11):1794-8. DOI: 10.1016/0959-8049(95)00383-T
Source: PubMed

ABSTRACT

Limited sampling models are able to estimate the area under the concentration-time curve (AUC) from plasma concentrations measured at only a few time points. The purpose of this study was to establish a model estimating etoposide AUC independently of specific chemotherapy protocols, underlying malignancies, concomitant diseases and age. Pharmacokinetic parameters were measured in 30 patients treated with polychemotherapy including etoposide (80-150 mg/m2). Etoposide analysis was performed by thin layer chromatography and consecutive quantitative sample detection by 252Cf-plasma desorption mass spectrometry. Data from the first 15 patients formed the training set. Based on the training data, five different models were generated, with the multiple regression coefficient r ranging from 0.91 to 0.96. The following model was selected as "most accurate": AUC = 343 (min)C4h(micrograms/ml) + 650(min)C8h(micrograms/ml) + 1252 (min micrograms/mol), where C4h is the plasma concentration of etoposide at 4 h after the end of infusion and C8h at 8 h. This model was validated on the test set, comprising the data of the remaining 15 patients. The mean predictive error (MPE) was -0.2% and the root mean square predictive error (RMSE) was 4.7%. When used for a large number of patients, this practicable and simple model is an instrument for use in prospective studies, to measure a correlation between drug dosage and efficacy or toxicity of the drug.

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    • "AUC is the best pharmacokinetic parameter for predicting anticancer pharmacodynamic effects. Precise estimation of AUC based on plasma concentration requires the handling of many blood samples, usually 8–12, which is expensive, time-consuming and inconvenient.12,106 Several limited sampling models (LSM) that are based only on a few sparse determinations of plasma concentrations and can obtain a good estimate of the AUC for oral etoposide, were developed and validated.107–109 "
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    No preview · Article · Feb 1999 · Cancer Chemotherapy and Pharmacology
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