Pharmacologic disposition of DL-alanosine in mice, rats, dogs, and monkeys

The pharmacologic disposition of DL-alanosine was studied in mice, rats, dogs, and monkeys. The major portion of the parenterally administered drug was excreted in the urine by all of the species studied; however, in rodents an important fraction of the dose was expired as CO2. Organs in which DL-alanosine accumulates include the kidneys, lungs, liver, and small intestine. Considerable drug-derived radioactivity persists for periods up to 14 days in the hepatic and renal parenchyma. Studies on the clearance of DL-alanosine in mice using a specific enzymatic assay procedure indicated that the plasma half-life of the parent drug was shorter than the half-life of total radioactivity. In both cases, however, the kinetics were complex and not readily resolvable into discrete phases. In murine lymphoblasts (L5178Y/AR) the transport of DL-alanosine was found to be a sodium-stimulated, saturable, and thermosensitive process which was inhibited by L-threonine, L-asparagine, L-glutamine, L-serine, L-leucine, L-isoleucine, L-valine, L-cysteine, and L-homoserine. Kinetic studies on the influence of L-asparagine and L-glutamine on this transport revealed that the inhibition was competitive in nature.