The effect of organic acids on renal clearance of methotrexate in man
| Autor: | A B Mary Anne Hahn, Edward S. Henderson, Vincent T. Oliverio, Donald G. Liegler |
|---|---|
| Rok vydání: | 1969 |
| Předmět: |
Male
Cancer chemotherapy Sodium Salicylate Inulin Biological Transport Active Renal function Plasma protein binding Pharmacology Tritium chemistry.chemical_compound Neoplasms medicine Humans Pharmacology (medical) Carbon Isotopes Inulin Clearance Leukemia Aminohippuric Acids Blood Proteins Middle Aged Kidney Tubules Methotrexate Minimal effect chemistry Colorimetry Female Sulfisoxazole Glomerular Filtration Rate Protein Binding Clearance medicine.drug |
| Zdroj: | Clinical Pharmacology & Therapeutics. 10:849-857 |
| ISSN: | 0009-9236 |
| Popis: | The renal clearance of the folic acid antagonist, methotrexate, was compared with that of inulin and para-aminohippurate in 15 patients with disseminated malignancy. The clearance of methotrexate exceeded that of inulin clearance in all cases, indicating methotrexate is not only filtered but is also actively secreted by the renal tubules. The simultaneous intravenous administration of weak organic acids resulted, generally, in suppressive effects on the clearance of methotrexate. Salicylate and high concentrations of para-aminohippurate reduced methotrexate clearance well below the glomerular filtration rate; whereas, sulfisoxazole had only a minimal effect on total methotrexate clearance. The variations of plasma protein binding of methotrexate induced by these same drugs did not correlate with the direction or degree of methotrexate clearance. It is concluded from these studies that methotrexate is excreted by a combination of glomerular filtration and active tubular transport and that methotrexate clearance is not directly related to the level of free methotrexate presented to the kidneys. It is furthermore suggested that the alterations in plasma protein binding and renal clearance of methotrexate provoked by the simultaneous administration of other organic acids may be clinically exploitable in cancer chemotherapy. |
| Databáze: | OpenAIRE |
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