Folate and methotrexate interactions in the rat kidney.
The mechanisms controlling the renal retention and urinary output of methotrexate and folates were studied in rats. 125I-Labeled folic acid administered i.v. was shown to be retained in the kidney through a system that could be inhibited by either folic acid or 5-methyltetrahydrofolate. Methotrexate also inhibited this system but required concentrations 50- to 100-fold greater than that required for folic acid and 5-methyltetrahydrofolate. Extracts from solubilized kidneys were shown to contain a folate binder with the same relative affinities for folates and methotrexate as the in vivo system. Methotrexate was shown to cause an increase in the urinary output of endogenous folates in rats when administered as equivalent doses to those used in treating human disease. Conversely, [3H]methotrexate administered i.v. was shown to be retained in the kidney through an additional system that could be inhibited by unlabeled methotrexate, but not by folates. This system was not demonstrable in solubilized kidney. These data demonstrate two systems for the renal retention of methotrexate.
Deutsch
J C
JC
University of Colorado Health Sciences Center, Denver 80262.
Kolhouse
J F
JF
D000818:Animals; D005492:Folic Acid / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008727:Methotrexate / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
D005492:Folic Acid; D008727:Methotrexate