[Relations between hematological toxicity and total and free plasma levels of etoposide in daily oral administration].

This study was undertaken in order to evaluate the inter- and intra-individual pharmacokinetic variabilities and their impact on the toxicity of oral Vépéside Sandoz administered daily for 21 days. The pharmacokinetic results confirmed the low bioavailability of this formulation (14% +/- 10%) and its large interindividual variability. Moreover, a great intraindividual variability was shown between day 1 and day 21. This fact can explain that the relationship between the relative decrease in neutrophil count and the pharmacokinetic parameters was observed only with either the mean area under the curve of concentrations versus time (AUC) or the mean residual concentrations (Cr). The determination of the fraction of plasma etoposide unbound, which ranged from 4.6 to 24.8%, improved the pharmacokinetic-pharmacodynamy relationship for AUC but not for Cr. This study showed the potential interest of etoposide drug monitoring. However, no dosage adjustment could be performed with this oral etoposide formulation because of its large intraindividual bioavailability. Since this study was performed, the Sandoz company withdrew this formulation, and replaced it by one identical with that available in other countries.