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Eur J Clin Pharmacol. 1975 Aug 14;8(6):439-44.

Renal function and the rate of disappearance of methotrexate from serum.

Abstract

The disappearance of methotrexate (MTX) from serum was studied using H3-MTX. The overall elimination half-life (MTX T1/2) was well defined from one to about six hours after i.v. administration; in 25 patients it ranged from 102 min to 750 min and was inversely related to endogenous creatinine clearance, which ranged from 6 to 140 ml/min. The corresponding apparent volume of distribution, V, obtained by extrapolation tended to decrease at lower levels of renal function. The total clearance of MTX calculated in this period varied linearly with creatinine clearance. In patients with normal serum creatinine concentration, the half-life increased with advancing age, which reflects the concurrent age-dependent decrease in creatinine production and renal function. This illustrates the need for knowledge of renal function, not based solely on serum creatinine concentration, in patients treated with methotrexate or other drugs eliminated by the kidneys. In 9 patients the results were not affected by treatment with diuretics (furosemide, hydroflumethiazide). In four patients serum MTX concentration was measured for up to 24-72 hours. An increasing half-life of MTX with time was found, suggesting that the elimination kinetics of the drug would be most adequately described by a multi-compartment model.

PMID:
1233246
DOI:
10.1007/bf00562319
[Indexed for MEDLINE]

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