Abstract
The pharmacokinetics and metabolism of intravenously infused 14C-fotemustine (about 100 mg/m 2) were examined in 2 cancer patients. Plasma levels of radioactivity increased to a maximum of 4.1 and 5.5 μg equivalents per g when the infusion stopped then declined triexponentially with mean half-lives of about 1 2 , 10 and 80 h for the initial, mid and terminal phases, respectively. Plasma levels of intact drug were lower, with maximum levels of 1.1 and 2.8 μg/ml, and declined monophasically with a half-life of about 24 min. Plasma clearance was high (1426 and 764 ml/min) with the volume of distribution based on areas of 47.7 and 26.4 1. Most of the radioactivity was eliminated in urine (50.1 and 61.3%) over 7 days with smaller amounts in the faeces (6.8 and 0.3%) and only minimal quantities (under 0.1%) as expired carbon dioxide. Metabolites of fotemustine were identified as chloroethanol and N-nitroso-1-imidazolone-ethyl-diethylphosphonate in plasma and as 1-hydantoin-ethyl-diethyl-phosphonate and acetic acid in urine.
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