Early studies of etoposide phosphate, a water-soluble prodrug

Abstract

Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble prodrug of etoposide that is converted in vivo by endogenous phosphatases to the active drug etoposide. This conversion process is efficient and not saturable in humans at doses between 50 and 1, 600 mg/m2. The resultant etoposide demonstrates classic pharmacokinetics, and the etoposide phosphate dose is linearly related to peak levels and the area under the concentration-time curve of etoposide. The absence of noxious solvents and the ability to administer the drug in small volumes over short periods make etoposide phosphate attractive for conventional- and high-dose clinical programs.