Pharmacokinetics of Teniposide (VM26) and etoposide (VP16-213) in children with cancer.
The clinical pharmacokinetics of VM26 and VP16-213 were assessed in 15 children (median age 10 years) with acute leukemia, using a new high-performance liquid chromatography-electrochemical assay. Pharmacokinetic parameters were calculated by both model-dependent and compartment model-independent methods. These studies demonstrated substantial differences in the central volumes of distribution (VDc), steady-state volumes of distribution (VDss) and systemic clearances (Cls) of VM26 and VP16-213; with the VDc, VDss, and Cls all being smaller for VM26, Systemic clearances determined by model-independent methods were 5.2 +/- 1.0 ml/min/m2 (mean +/- SD) for VM26 and 17.8 +/- 11.2 ml/min/m2 for VP16-213. The major metabolites. detected in serum and urine were the hydroxy acids. Low levels of the picro-lactone isomers were detected in some patients while the aglycones were not detected in the serum or urine of any patients.
D001711:Biotransformation; D002648:Child; D002851:Chromatography, High Pressure Liquid; D005047:Etoposide / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D007938:Leukemia / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D013713:Teniposide / Q000378:metabolism*
D005047:Etoposide; D013713:Teniposide; D011034:Podophyllotoxin