title: Metabolism and biliary excretion of trimetrexate by the isolated perfused rat liver.
abstract: The metabolism and biliary excretion of trimetrexate (TMTX), a lipid soluble antifolate, were examined using a recirculating isolated perfused rat liver system. Elimination of TMTX into perfusate was biphasic and dose-independent, with distribution and elimination half-lives of 2 and 13 min. Two metabolites, M1 and M2, both known to inhibit dihydrofolate reductase activity, were present in perfusate only in small concentrations. However, of the total TMTX dose, approximately 50% was excreted in bile as M1, and 20% as M2. Up to 75% of the total dose was accounted for as TMTX, M1, or M2 in perfusate and bile.
authors.forename: L K
authors.initials: LK
authors.lastname: Webster
authors.forename: W P
authors.initials: WP
authors.lastname: Tong
authors.forename: J J
authors.initials: JJ
authors.lastname: McCormack
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005493:Folic Acid Antagonists / Q000378:metabolism*; D006207:Half-Life; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011799:Quinazolines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016597:Trimetrexate
chemical_list: D005493:Folic Acid Antagonists; D011799:Quinazolines; D016597:Trimetrexate