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.
D000409:Alanine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000378:metabolism*; D001224:Aspartic Acid / Q000037:antagonists & inhibitors; D002245:Carbon Dioxide / Q000378:metabolism; D002415:Cats; D002478:Cells, Cultured; D004285:Dogs; D005260:Female; D000882:Haplorhini; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D007942:Leukemia, Experimental / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009602:Nitrosamines / Q000097:blood / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D013696:Temperature
D000903:Antibiotics, Antineoplastic; D009602:Nitrosamines; D002245:Carbon Dioxide; C000082:alanosine; D001224:Aspartic Acid; D012964:Sodium; D000409:Alanine