Teniposide is a phase-specific cytotoxic drug, acting in the late S or early G ₂ phase of the cell cycle, thus preventing cells from entering mitosis.

Teniposide causes dose-dependent single- and double-stranded breaks in DNA and DNA: protein cross-links. The mechanism of action appears to be related to the inhibition of type II topoisomerase activity since teniposide does not intercalate into DNA or bind strongly to DNA. The cytotoxic effects of teniposide are related to the relative number of double-stranded DNA breaks produced in cells, which are a reflection of the stabilization of a topoisomerase II-DNA intermediate.

Teniposide has a broad spectrum of in vivo antitumor activity against murine tumors, including hematologic malignancies and various solid tumors. Notably, teniposide is active against sublines of certain murine leukemias with acquired resistance to cisplatin, doxorubicin, amsacrine, daunorubicin, mitoxantrone or vincristine.

Plasma drug levels declined biexponentially following intravenous infusion (155 mg/m ² over 1 to 2.5 hours) of VUMON given to eight children (4-11 years old) with newly diagnosed acute lymphoblastic leukemia (ALL). The observed average pharmacokinetic parameters and associated coefficients of variation (CV%) based on a two-compartmental model analysis of the data are as follows:

There appears to be some association between an increase in serum alkaline phosphatase or gamma glutamyl-transpeptidase and a decrease in plasma clearance of teniposide. Therefore, caution should be exercised if VUMON is to be administered to patients with hepatic dysfunction.

In adults, at doses of 100 to 333 mg/m ² /day, plasma levels increased linearly with dose. Drug accumulation in adult patients did not occur after daily administration of VUMON for 3 days. In pediatric patients, maximum plasma concentrations (C _max ) after infusions of 137 to 203 mg/m ² over a period of one to two hours exceeded 40 µg/mL; by 20 to 24 hours after infusion plasma levels were generally < 2µg/mL.

Renal clearance of parent teniposide accounts for about 10 percent of total body clearance. In adults, after intravenous administration of 10 mg/kg or 67 mg/m ² of tritium-labeled teniposide, 44 percent of the radiolabel was recovered in urine (parent drug and metabolites) within 120 hours after dosing. From 4 to 12 percent of a dose is excreted in urine as parent drug. Fecal excretion of radioactivity within 72 hours after dosing accounted for 0 to 10 percent of the dose.

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