Pharmacokinetics of amifostine: effects of dose and method of administration.

Abstract Findings of pharmacokinetic studies of amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) in animal models and in human cancer patients support the hypothesis that amifostine pharmacokinetics are nonlinear. The nonlinear pharmacokinetic behavior of amifostine suggests that administration of doses higher than 740 mg/m2 does not increase the amount of drug available due to urinary excretion of the excess parent drug and its metabolites. Although the intravenous formulation of amifostine is the only one currently used in the treatment of cancer patients, there is growing interest in the investigation of subcutaneous administration as a practical alternative. A pilot pharmacokinetic evaluation of subcutaneous administration of amifostine in 12 healthy male volunteers compared the relative bioavailability of 500 mg of amifostine administered subcutaneously with that of 200 mg/m2 given intravenously.