Pharmacokinetics of high-dose teniposide.
This paper describes the pharmacokinetics of teniposide (VM-26) after being administered iv in high doses to eight cancer patients (maximum dose, 1.0 g/m2). VM-26 levels in plasma, urine, saliva, duodenal fluid, and cerebrospinal fluid were determined using high-performance liquid chromatography in combination with electrochemical detection. The plasma concentration-time curve of VM-26 showed a triphasic decay with a slow third phase in five patients, whereas in two patients the plasma concentration decay was biphasic. The plasma pharmacokinetics of VM-26 proved to be linear and could be fitted to a three-compartment model (five patients) and to a two-compartment model (two). The steady-state volume of distribution varied from 13.2 to 24.7 L/m2. The total-body clearance ranged from 5.84 to 10.18 ml/minute/m2. Low concentrations of VM-26 were found in saliva, duodenal fluid, cerebrospinal fluid, and urine. Excretion of unchanged VM-26 into the urine varied from 8.8% to 13.9% of the administered dose. No glucuronide of VM-26 could be detected in plasma or other biological fluid.
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D013713:Teniposide / Q000008:administration & dosage / Q000378:metabolism*
D013713:Teniposide; D011034:Podophyllotoxin