The disposition of spirohydantoin mustard (NSC 172112) in rats and dogs

1. The disposition of spirohydantoin mustard (SHM) has been examined in rats and dogs after i.v. administration of (hydantoin-4-14C]SHM and [2-chloroethyl-U-14C]SHM. 2. Four hours after dosing to rats and dogs, renal clearance of the ethyl-14C moiety (14--21%) is lower than that of the hydantoin-14C moiety (29--68%). In contrast, biliary excretion of the ethyl-14C in rats is greater, and there appears to be enterohepatic circulation of the ethyl-14C. 3. Less than 1% of the radioactivity appearing in rat bile is unchanged SHM. Two major metabolites containing the ethyl-14C moiety are conjugates of glutathione or cysteine. 4. Levels of 14C in plasma decline in a biphasic manner. No difference in the initial plasma disappearance of the two labelled moieties is observed, but disappearance of the ethyl-14C During the second phase is slower. 5. Concentrations of ethyl14C and hydantoin-14C in the brains of rats and dogs, 4 h after i.v. administration, are equivalent to those in plasma. 6. Radioactivity is also distributed to the brain of rats after oral administration of [2-chloroethyl-J-14C]SHM, but at a concn. less than half that of plasma.