Disposition of an Antineoplastic Sesquiterpene Lactone, [³ H]-Plenolin, in BDF₁ Mice

Abstract

The pharmacokinetics of a radiolabelled analog of helenalin, [³ H]-plenolin ([³ H]-11,13-dihydrohelenalin), was determined in BDF₁ mice following intravenous, intraperitoneal, and oral administration. A two-compartment pharmacokinetic model predicted that the maximum terminal (beta) half-life of [³ H]-plenolin was 57.3 hours. Urinary excretion accounted for 40.3% to 64.4% of the administered radioactivity, while fecal excretion accounted for 9.3% to 39.7%. The fecal excretion data also suggested that [³ H]-plenolin was secreted in the bile. Following intraperitoneal administration of [³ H]-plenolin, no radioactivity was sequestered in the major organs. However, radioactivity was sustained in the carcass and skin for 24 days. [³ H]-Plenolin was rapidly taken up by murine tumor cells and human fibroblasts. The drug did not significantly associate with DNA, RNA, or protein of P388 leukemia or human fibroblast cells.

Key words

Antineoplastic sesquiterpene - pharmacokinetics - helanalin - [³ H]-plenolin - Helenium genus