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Drug monitoring of etoposide (VP16-213)

Correlation of pharmacokinetic parameters to clinical and biochemical data from patients receiving etoposide

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Summary

Pharmacokinetic parameters established in 15 patients receiving parenterally administered etoposide (80–120 mg·m-2) are reported. The etoposide assay by means of mass spectrometry after sample separation by thin-layer chromatography or high-pressure liquid chromatography used in this study has been described else-where [4]. Peak plasma levels (9.5–63.3 μg·ml-1), the area under the curve (AUC) (2707–10192 μg·ml-1·min-1), the mean transit time MTT (2.7–10.6 h), etoposide half-lives t1/2α (0.10–0.52 h) and t1/2β (2.18–8.17 h), the volume of distribution at steady state (Vdss) (2.5–15.1·l/m-2) and the systemic clearance (Cls) (10.1–35.1 ml min-1·m-2) with the resulting mean values and standard deviations were determined. Our findings are compared with those of other authors, especially with regard to the method of detection used. This comparison indicates similar individual deviations and shorter half-lives with increasing specificity of the employed assay. Four patients studied on 3 consecutive days and, in one instance, during two different cycles of chemotherapy showed no sign of accumulation or of accelerated excretion of etoposide. There was little intrapatient variability. The pharmacokinetic parameters were correlated to clinical and laboratory findings. Statistical analysis indicated that the AUC was increased by prior cisplatin therapy and in patients with elevated levels of alkaline phosphatase. The Cls was decreased by prior cisplatin therapy, in obese patients, and by elevated alkaline phosphatase. The t1/2β of etoposide was increased in older patients. Linear regression analysis yielded a grater Vdss in patients with lower serum albumin levels, but this correlation has not yet been found to be statistically significant.

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Correspondence to Karl-Heinz Pflüger.

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Pflüger, K., Schmidt, L., Merkel, M. et al. Drug monitoring of etoposide (VP16-213). Cancer Chemother. Pharmacol. 20, 59–66 (1987). https://doi.org/10.1007/BF00252961

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Keywords

  • Alkaline Phosphatase
  • Obese Patient
  • Etoposide
  • Pharmacokinetic Parameter
  • Transit Time