Pharmacokinetics of VP16-213 given by different administration methods

Area of Science:

• Pharmacology
• Clinical Pharmacology
• Oncology

Background:

• Etopophos (VP-213) is an anticancer drug.
• Understanding its pharmacokinetic profile is crucial for optimizing treatment.
• Previous studies have not fully elucidated its behavior in different patient populations and administration routes.

Purpose of the Study:

• To investigate the plasma pharmacokinetics of VP-213 in adult and pediatric patients.
• To evaluate the bioavailability of oral VP-213 formulations.
• To determine VP-213 levels in cerebrospinal fluid (CSF).

Main Methods:

• Pharmacokinetic analysis of VP-213 plasma concentrations after intravenous infusion in adults and children.
• Assessment of VP-213 bioavailability via oral capsules and drinkable ampoules compared to intravenous administration.
• Measurement of VP-213 levels in CSF following intravenous and oral administration.

Main Results:

• Adults: T1/2 beta = 7.05 h, Clp = 26.8 ml/min/m2, Vd = 15.7 l/m2. Children: T1/2 beta = 3.37 h, Clp = 39.34 ml/min m2, Vd = 9.97 l/m2.
• No VP-213 accumulation observed after repeated daily doses.
• Oral bioavailability varied (57% capsules, 91% ampoules); levels were undetectable in one patient with malabsorption.
• CSF levels of VP-213 were undetectable after both IV and oral administration.

Conclusions:

• VP-213 exhibits distinct pharmacokinetic parameters in adults and children.
• Oral formulations offer variable but potentially viable routes of administration.
• Limited CSF penetration suggests VP-213 may not be effective for central nervous system malignancies.