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Renal Tubular Transport of Methotrexate in the Rhesus Monkey and Dog¹

Department of Pharmacology and Toxicology [K.C.H., B.A.W.] and Department of Medicine [Y.K.L.], University of Louisville, Health Sciences Center, Louisville, Kentucky 40232

The mechanism and localization of renal transport of methotrexate (MTX) were studied in the rhesus monkey and the dog. It was found that in both animals MTX was bound with plasma protein in a range of 50 to 68% varying with the MTX plasma concentration. Paper chromatographic analysis showed that a negligible amount of MTX was metabolized. The excretion of MTX in rhesus monkey was mainly by tubular secretion which was blocked by probenecid, but in the dog a bidirectional transport mechanism for MTX was indicated. Tubular secretion was localized in the proximal tubules, and a tubular reabsorptive process was in the distal section. Simultaneous administration of folic acid blocked the tubular reabsorption of MTX, resulting in an increase of renal excretion. Maximum tubular excretory capacity determination showed that a maximum tubular excretory capacity value of approximately 5 µmol/100 ml of glomerular filtrate was observed in the rhesus monkey at a plasma concentration of 0.07 mM and a value of 2 µmol/100 ml of glomerular filtrate for the dog. Studies with renal cortical slice technique also indicated that the monkey kidney can accumulate greater amounts of MTX than can the dog kidney.

¹ Supported in part by USPHS Grant CA 25252-01. A preliminary report has appeared (6).

² To whom requests for reprints should be addressed, at University of Louisville Health Sciences Center, Louisville, Ky. 40232.

³ Recipient of a fellowship awarded by the University of Louisville Graduate School and American Cancer Society Institutional Grant IN-111C.

Received 11/15/78. Accepted 8/21/79.

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