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

Abstract The pharmacokinetics of a radiolabelled analog of helenalin, [ 3 H]-plenolin ([ 3 H]-11,13-dihydrohelenalin), was determined in BDF 1 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.