Inadults, at doses of 100 to 333 mg/m/day, plasmalevels increased linearly with dose. Drug accumulation in adult patients didnot occur after daily administration of VUMON for 3 days. In pediatric patients,maximum plasma concentrations (C) after infusionsof 137 to 203 mg/m over a periodof 1 to 2 hours exceeded 40 mcg/mL; by 20 to 24 hours after infusion plasmalevels were generally <2 mcg/mL.

Renal clearanceof parent teniposide accounts for about 10% of total body clearance. In adults,after intravenous administration of 10 mg/kg or 67 mg/m oftritium-labeled teniposide, 44% of the radiolabel was recovered in urine (parentdrug and metabolites) within 120 hours after dosing. From 4% to 12% of a doseis excreted in urine as parent drug. Fecal excretion of radioactivity within72 hours after dosing accounted for 0% to 10% of the dose.

Meansteady-state volumes of distribution range from 8 to 44 L/m foradults and 3 to 11 L/m for children. The blood-brainbarrier appears to limit diffusion of teniposide into the brain, althoughin a study in patients with brain tumors, CSF levels of teniposide were higherthan CSF levels reported in other studies of patients who did not have braintumors.

Teniposide is highly protein bound. Invitro plasma protein binding of teniposide is >99%. The high affinityof teniposide for plasma proteins may be an important factor in limiting distributionof drug within the body. Steady-state volume of distribution of the drug increaseswith a decrease in plasma albumin levels. Therefore, careful monitoring ofchildren with hypoalbuminemia is indicated during therapy. Levels of teniposidein saliva, CSF, and malignant ascites fluid are low relative to simultaneouslymeasured plasma levels.

The pharmacokinetic characteristicsof teniposide differ from those of etoposide, another podophyllotoxin. Teniposideis more extensively bound to plasma proteins and its cellular uptake is greater.Teniposide also has a lower systemic clearance, a longer elimination half-life,and is excreted in the urine as parent drug to a lesser extent than etoposide.

Ina study at St. Jude Children's Research Hospital (SJCRH), 9 children withacute lymphocytic leukemia (ALL) failing induction therapy with a cytarabine-containingregimen, were treated with VUMON plus cytarabine. Three of these patientswere induced into complete remission with durations of remission of 30 weeks,59 weeks, and 13 years. In another study at SJCRH, 16 children with ALL refractoryto vincristine/prednisone-containing regimens were treated with VUMON plusvincristine and prednisone. Three of these patients were induced into completeremission with durations of remission of 5.5, 37, and 73 weeks. In these 2studies, patients served as their own control based on the premise that long-termcomplete remissions could not be achieved by re-treatment with drugs to whichthey had previously failed to respond.

Parameter  Mean  CV% 
Total body clearance (mL/min/m2) 10.3 25
Volume at steady-state (L/m2) 3.1 30
Terminal half-life (hours) 5.0 44
Volume of central compartment (L/m2) 1.5 36
Rate constant, central to peripheral (1/hours) 0.47 62
Rate constant, peripheral to central (1/hours) 0.42 37

VUMON (teniposide injection), in combination with other approved anticancer agents, isindicated for induct