Pharmacokinetics of VP16-213 in Lewis lung carcinoma bearing mice.

The pharmacokinetics of VP16 have been investigated in Lewis lung bearing mice after i.v. doses of 13 and 40 mg/kg. At both doses the plasma elimination of half-life was around 30 min. The lowest VP16-213 levels were in brain and primary tumor. Drug concentrations were much higher in metastases than in primary tumor. The highest concentrations were in small intestine, liver and kidney. Drug levels in the liver were disproportionally higher after 40 mg/kg, and AUC value being approximately 12 times greater than after 13 mg/kg. Urinary excretion of VP16-213 as unchanged drug accounted for 20-30% of the administrated dose in the 60 h after treatment. The concentration cytotoxicity curve was very steep and apparently similar for cells derived from primary tumor or metastases grown in vitro.