Summary
The plasma concentration and urinary excretion of methotrexate were followed in twelve psoriatic patients after intravenous and oral doses of methotrexate ranging from 7.5 to 30 mg. In six of the patients, a nonlinear relation was found between the fractional amount of methotrexate excreted in the urine and the corresponding area under the plasma concentration-time curve. The methotrexate clearance was found to be increased during the initial high plasma concentration, probably due to saturation of the tubular reabsorption of methotrexate. Considerable interindividual variation was found in the apparent saturation point of the active reabsorption, but up to 500–800 ng/ml first order kinetics still applied. At plasma concentrations below saturation, the renal clearance of methotrexate ranged from 52–102 ml/min (mean±SD, 83±19.4 ml/min).
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Goldie JH, Price LA, Harrap KR (1972) Methotrexate toxicity: Correlation with duration of administration, plasma levels, dose and excretion pattern. Eur J Cancer 8: 409–414
Goresky CA, Watanabe H, Johns DC (1963) The renal excretion of folic acid. J Clin Invest 42: 1841–1849
Hendel J, Sarek LJ, Hvidberg EF (1976) Rapid radioimmunoassay for methotrexate in biological fluids. Clin Chem 22: 813–816
Huffman DH, Wan SK, Azarnoff DL, Hoogstraten B (1973) Pharmacokinetics of methotrexate. Clin Pharmacol Ther 14: 572–579
Lawrence JR, Steele WH, Stuart JFB, McNeill CA, McVie, Whiting B (1980) Dose dependent methotrexate elimination following bolus intravenous injection. Eur J Clin Pharmacol 17: 371–374
Leme PR, Creaven PJ, Allen LM, Bergman M (1975) Kinetic model for the disposition and metabolism of moderate and high dose methotrexate (NSC-740) in man. Cancer Chemother Rep 59: 811–817
Liegler DG, Henderson ES, Hahn MA, Oliverio VT (1969) The effect of organic acids on renal clearance of methotrexate in man. Clin Pharmacol Ther 10: 849–857
Nyfors A (1980) Methotrexate therapy of psoriasis. Dan Med Bull 27: 74–96
Reich DS, Bachur NR, Goebel RH, Bergman M (1977) A pharmacokinetic model for high-dose methotrexate infusions in man. J Pharmacokinet Biopharm 5: 421–433
Salasoo S, Irving MG, Freedman A (1976) Methotrexate megadose followed by folate rescue II. Clearance patterns in patients receiving sequential megadose infusions. Med J Austral i: 826–828
Shen DD, Azarnoff DL (1978) Clinical Pharmacokinetics of methotrexate. Clin Pharmacokinet 3: 1–13
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Hendel, J., Nyfors, A. Nonlinear renal elimination kinetics of methotrexate due to saturation of renal tubular reabsorption. Eur J Clin Pharmacol 26, 121–124 (1984). https://doi.org/10.1007/BF00546719
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DOI: https://doi.org/10.1007/BF00546719