Tissue and Organ Distribution of Etoposide in Rat

Abstract

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 lymphoma. We have studied the tissue and organ distribution of [³H]-Etoposide by whole body autoradiography and quantitative determination of radioactivity in the tissues and organs of rats. [³H]-Etoposide distributed mainly in the liver, intestine and kidney. It was in good agreement with the fact that [³H]-Etoposide was mainly excreted into the bile in the case of rat. No [³H]-Etoposide was found in the brain after a single administration, it was regarded that Etoposide almost did not penetrate through the blood-brain barrier. Only a slight radioactivity was found in the brain after the consecutive p.o. administration for 10 days. When [³H]-Etoposide was administered to the pregnant rats, radioactivity was found in the fetus in concentration about 1/10 of maternal blood level. In the consecutive administration, the concentration in most tissues and organs was higher than that after single administration, whereas the half-lives in these organs (β-phase) were not prolonged. One may conclude, concerning the above fact, that Etoposide did not accumulate in tissues and organs.