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- W2073593907 abstract "The pharmacokinetics and metabolism of dibutyl methotrexate (DBMTX) and gamma-monobutyl methotrexate (gamma-MBMTX) were studied in Rhesus monkeys. When a bolus IV dose of either [3H]DBMTX or [3H] gamma-MBMTX was given, the principal species in serum for up to 1 h was the monoester, with MTX accounting for less than 10% of the total radioactivity. Products other than gamma-MBMTX and MTX were formed in substantial amounts with DBMTX, but not with gamma-MBMTX. Total radioactivity recovered in the bile 5 h after [3H]DBMTX injection accounted for 32% of the administered dose, indicating high hepatic extraction for this lipophilic compound. Serum and CSF levels of unchanged gamma-MBMTX, as well as of MTX arising via esterase cleavage, were measured by HPLC after IV infusion of gamma-MBMTX (10 g/m2). Efflux of monoester from CSF was slower than disappearance from serum. However, gamma-MBMTX levels in CSF were no higher than could be attained by infusing MTX itself at the same dose rate. While CSF/serum ratios were ca. 10-fold higher for gamma-MBMTX than for MTX, this difference could be explained on the basis of the very different affinities of the two compounds for serum proteins. HPLC analysis of serum processed by methanol precipitation as opposed to ultrafiltration of the proteins showed gamma-MBMTX to be greater than 99% bound, whereas for MTX this value was 50% or less. When gamma-MBMTX and MTX levels measured after ultrafiltration were corrected for this difference in serum protein binding the total amount of the two drugs in serum became almost equivalent." @default.
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- W2073593907 date "1982-12-01" @default.
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- W2073593907 title "Pharmacologic studies on the dibutyl and ?-monobutyl esters of methotrexate in the rhesus monkey" @default.
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- W2073593907 doi "https://doi.org/10.1007/bf00257240" @default.
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