Renal tubular transport of folic acid and methotrexate in the monkey.
The renal excretion of folic acid and methotrexate (MTX) was investigated in pentobarbital-anesthetized cynomolgus, rhesus, and AFrican green monkeys by standard clearance and stop-flow techniques. The renal clearance of folic acid was below inulin clearance at all plasma concentrations studied; the (U/P)folic/(U/P)In ratio increased from 0.26 at a concentration of 0.03 mM to a plateau value of 0.9 at concentrations above 0.2 mM, indicating net reabsorption by a saturable system. In stop-flow experiments, base-line (U/P)folic/(U/P)In ratios during free-flow periods were below 1.0, but increased by twofold in stop-flow samples derived from the proximal tubule, indicating net secretion during stopped flow. The stop-flow pattern of MTX excretion was similar, except the base-line flow pattern of MTX excretion was similar, except the base-line (U/P)MTX/(U/P)In ratio exceeded 1.0, indicating net secretion during both free-flow and stopped-flow periods. Secretion of both compounds was inhibited by p-aminohippuric acid and other organic acids but not by L-glutamic acid. It is concluded that folic acid is transported bidirectionally, while evidence was obtained only for secretion of MTX.
D000818:Animals; D001692:Biological Transport; D002522:Chlorocebus aethiops; D005492:Folic Acid / Q000378:metabolism*; D006706:Homeostasis; D007684:Kidney Tubules / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism
D011506:Proteins; D005492:Folic Acid; D008727:Methotrexate