Disposition of an antineoplastic sesquiterpene lactone, [3H]-plenolin, in BDF1 mice.

The pharmacokinetics of a radiolabelled analog of helenalin, [3H]-plenolin ([3H]-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 [3H]-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 [3H]-plenolin was secreted in the bile. Following intraperitoneal administration of [3H]-plenolin, no radioactivity was sequestered in the major organs. However, radioactivity was sustained in the carcass and skin for 24 days. [3H]-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.