1986 Volume 1 Issue 2 Pages 123-142
Etoposide {4'-demethylepipodophyllotoxin-9 (4, 6-O-ethylidene-β-D-glucopyranoside)}, an anticancer drug, is a semisynthetic derivative of podophyllotoxin, and it is claimed to be effective in a lung and testis cancer and in a lymphoma. We have synthesized a tritium labeled Etoposide ([3H]-Etoposide) for the pharmacokinetics study. The blood concentration of [3H]-Etoposide in dog was decreased relatively fast in a tri-exponential pattern following i.v. injection. The blood level of [3H]-Etoposide in dog reached to a maximum level i.v. or p.o. administration, and then it diminished relatively rapidly in a biexponential manner from the blood. Bioavailability in dog after p.o. administration was 13.1 % calculated from the AUC after i.v. and p.o. administration. Cumulative excretion following i.v. and p.o. administration were 75 and 86 %, respectively. The blood concentration of [3H]-Etoposide was same both in rats and dogs, and bioavailability was 14.1 % obtained from the AUC data. The half-life of β-phase after the consecutive i.v. injection was prolonged to about 2 times than that after a single injection. The total excreted amounts to urine and feces were 95 % during 72 hours after a single and consecutive injection, indicating that excreted amount (% of administered dose) was not changed by the consecutive administration. [3H]-Etoposide was mainly excreted into the bile in rats, and 68.1 and 33.8 % of it was excreted into the bile after i.v. and p.o., respectively, during 72 hours after administration. The reabsorption rate of [3H]-Etoposide in rat was 9.3% of i.v. administered dose and 12.5 % after p.o. administration. The absorption rate of [3H]-Etoposide in rat was about 40 % calculated from the total excretion in urine and bile after p.o. administration. [3H]-Etoposide was also excreted into the milk to higher extent than to the blood. This was regarded to be due to the high lipophilicity of Etoposide.
