Short communicationPhase I and pharmacokinetic study of a water-soluble etoposide prodrug, Etoposide phosphate (cas 117091-64-2) (BMY-40481)

Add time:08/31/2019    Source:sciencedirect.com

Etoposide phosphate (cas 117091-64-2) is a water-soluble prodrug of etoposide. A phase I and pharmacokinetic study has been performed over the dose range 25–110 mg/m2/day for 5 days (etoposide equivalent doses). The maximum tolerated dose (MTD) was 110 mg/m2/day for 5 days every 3 weeks and the dose-limiting toxicity was neutropenia. Other toxicities were mild, with the exception of 2 patients who displayed significant hypersensitivity reactions. The etoposide phosphate:etoposide area under the plasma concentration versus time curve (AUC) ratio was <1% and the pharmacokinetic parameters for etoposide were within previously reported ranges. Pharmacodynamic analyses demonstrated that etoposide AUC and baseline white blood cell count were significant determinants of leucopenia (model r2 = 0.51).

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