A limited sampling model for the pharmacokinetics of etoposide given orally |
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Authors: | Donatella Gentili Massimo Zucchetti Valter Torri Cristiana Sessa Jolanda de Jong Franco Cavalli Maurizio D'Incalci |
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Institution: | (1) Mario Negri Institute for Pharmacological Research, Via Eritrea 62, I-20157 Milan, Italy;(2) Division of Oncology, Ospedale San Giovanni, CH-6500 Bellinzona, Switzerland |
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Abstract: | A limited sampling model of etoposide after oral administration to estimate the area under the plasma concentration-time curve from 0 to 24 h (AUC) by determination of the drug plasma levels at only two time points was developed by a multiple regression analysis on a training data set of 15 patients receiving oral doses ranging from 54 to 90 mg/m2. The equation describing the model is AUC (g ml–1 h)=5.183 (g ml–1 h)+1.193 (h)×C1h (g/ml)+8.439 (h)×C4h (g/ml) (R
2=0.93,P=0.0001), whereC
1h
andC
4h
represent the plasma etoposide concentrations at 1 and 4 h, respectively. The model was validated prospectively on a test data set of 13 patients receiving oral doses ranging from 52 to 87 mg/m2 and, additionally, on a data set of 7 patients receiving oral doses ranging between 176 and 200 mg/m2, investigated in a previous study. Validation on both test data sets gave a relative mean predictive error of 0.1% and a relative root mean square error of 15.8% and 16.7%, respectively. The present study shows that it is possible to obtain a good estimate of the plasma AUC after oral administration of etoposide using a two-time-point sampling model. The model can be used to monitor the etoposide AUC in patients receiving chronic oral treatment. |
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