Activity and pharmacokinetics of teniposide in Lewis lung carcinoma-bearing mice

Abstract

The antitumor activity of teniposide (VM26) was investigated in Lewis lung carcinoma (3LL) of the mouse after a single dose of 20 mg/kg iv (given 8 or 14 days after tumor transplant) or after three doses of 6.5 mg/kg iv (given on Days 8, 11, and 14 after tumor transplant) (total dose, 19.5 mg/kg). The single dose resulted in only 25% primary tumor reduction but had marked antimetastatic activity. The repeated doses (6.5 mg/kg x 3) were much more effective, with 85% primary tumor reduction and the apparent disappearance of all metastatic deposits. The pharmacokinetics of VM26 was investigated in 3LL-bearing mice by a high-performance liquid chromatographic assay. At both of the above doses VM26 disappeared from mouse plasma biphasically, with an elimination half-life of about 70 mins. The concentrations in metastases were higher than in primary tumor, where very low levels were found. The highest VM26 levels were found in liver, small intestine, and kidney, and the lowest levels were found in the brain. Excretion of VM26 in urine amounted to less than 5% of the dose.