TY - JOUR
T1 - Metabolism and biliary excretion of trimetrexate by the isolated perfused rat liver
AU - Webster, Lorraine K.
AU - Tong, William P.
AU - McCormack, John J.
N1 - Funding Information:
The authors gratefully acknowledge the excellent computer programs and assistance with data analysis provided by Dr. G.A. McPherson. This work was supported by NC1 Grants CA22435 and CA24543.
PY - 1985/10
Y1 - 1985/10
N2 - 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 doseindependent, 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.
AB - 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 doseindependent, 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.
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U2 - 10.1016/0304-3835(85)90124-7
DO - 10.1016/0304-3835(85)90124-7
M3 - Article
C2 - 2933139
AN - SCOPUS:0022410039
SN - 0304-3835
VL - 29
SP - 65
EP - 71
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -