Summary
Hydration and urinary alkalinization are used with high doses of methotrexate (MTX) to prevent precipitation of the drug in the renal tubules and consequential nephrotoxicity. The quantitative effect of these measures on the renal clearance of MTX was studied in 8 patients with normal renal function, and in 3 patients with reduced renal function. Multiple regression analysis indicated an influence of both factors on the ratio of the renal clearances of MTX and creatinine. In the eleven patients there was a linear correlation between this ratio and urine pH (p<0.001); the ratio increased from 0.88 at pH 5.5 to 2.62 at pH 8.4. The pH effect on this ratio was similar in the patients with normal and reduced kidney function. An increase in urine flow did not significantly increase the ratio between renal clearance of MTX and creatinine. The effect of urinary alkalinization on renal MTX clearance could be clinically exploited in patients with delayed elimination of MTX. The probable modifying effect of alkalinization of urine on the intentionally high plasma concentration after high dose MTX infusions should be further evaluated, particularly in patients with normal renal function.
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References
Jaffe N, Frei E III, Traggis D, Bishop Y (1974) Adjuvant methotrexate and citrovorum factor treatment of ostegenic sarcoma. N Engl J Med 291: 994–997
Djerassi I, Kim JS (1976) Methotrexate and citrovorum factor rescue in the management of childhood lymphosarcoma and reticulum cell sarcoma (non-Hodgkin's lymphomas). Prolonged unmaintained remission. Cancer 38: 1043–1051
Levitt M, Mosher MS, Deconti RC (1973) Improved therapeutic index of methotrexate with “leucovorin rescue”. Cancer Res 33: 1729–1734
von Hoff DD, Penta JS, Helman LJ, Slavik M (1977) Incidence of drug-related death secondary to high-dose methotrexate and citrovorum factor administration. Cancer Treat Rep 61: 745–748
Stoller RG, Jacobs SA, Drake JC, Lutz RJ, Chabner BA (1975) Pharmacokinetics of high-dose methotrexate (NSC-740). Cancer Chemother Rep 6: 19–24
Stoller RG, Hande KR, Jacobs SA, Rosenberg SA, Chabner BA (1977) Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity. N Engl J Med 297: 630–634
Nirenberg A, Mosende C, Metha BM, Gisolfi AL, Rosen G (1977) High-dose methotrexate with citrovorum factor rescue: predictive value of serum methotrexate concentrations and corrective measures to avert toxicity. Cancer Treat Rep 61: 779–783
Salassoo S, Irving MG, Freedman A (1975) Methotrexate megadose followed by folate rescue II Clearance patterns in patients receiving sequential megadose infusions. Med J Aust 1: 826–828
Bloomer HA (1966) A critical evaluation of diuresis in the treatment of barbiturate intoxication. J Lab Clin Med 67: 898–905
Weiner IM, Washington JA II, Mudge GH (1959) Studies on the renal excretion of salcylate in the dog. Bull Johns Hopkins Hosp 105: 284–297
Kamen BA, Takach PL, Vatev R, Caston JC (1976) A rapid radiochemical-ligand binding assay for methotrexate. Anal Biochem 70: 54–63
Gibaldi M, Perrier D: In: Swarbrick J (ed) Drugs and pharmaceutical sciences. Vol 1: Pharmacokinetics. Marcel Dekker, New York
Nilsen OG, Jacobsen S (1975) The binding of quinidine to protein fractions of normal human sera. Biochem Pharmacol 24: 995–998
Gornall AG, Bardawill CJ, David MM (1949) Determination of serum proteins by means of the Biuret reaction. J. Biol Chem 177: 751–766
Dettli L (1976) Drug dosage in renal disease. Clin Pharmacokinet 1: 81–98
Zaharko DS, Dedrick RL: In: Acheson EG (ed) Pharmacology and the future of man, Vol 3. S Karger, Basel, p 316
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Sand, T.E., Jacobsen, S. Effect of urine pH and flow on renal clearance of methotrexate. Eur J Clin Pharmacol 19, 453–456 (1981). https://doi.org/10.1007/BF00548590
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DOI: https://doi.org/10.1007/BF00548590