期刊
DRUG METABOLISM AND PHARMACOKINETICS
卷 21, 期 6, 页码 485-491出版社
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.2133/dmpk.21.485
关键词
methotrexate; 7-hydroxymethotrexate; aldehyde oxidase; in vivo metabolism; rat strain difference
The in vivo metabolism of methotrexate (MTX) to 7-hydroxymethotrexate (7-OH-MTX) was studied using four strains of rats. When MTX was administered to these rats, 7-OH-MTX was detected as the major in vivo metabolite, mainly in bile and feces, and also slightly in the urine. There were marked strain differences in the amounts of 7-OH-MTX excreted in bile, feces and urine. The highest recovery of 7-OH-MTX in bile, feces and urine was observed in Sea:SD rats (6.2%, 4.2% and 0.8% of dose, respectively), followed by Jcl:SD and Crj:SD rats. The lowest recovery (0.02%, 0.2% and 0.003%, respectively) was observed in WKA/Sea rats. The variations of excreted amount of 7-OH-MTX were closely correlated with the strain differences of cytosolic MTX 7-hydroxylase and benzaldehyde oxidase activities. Our results indicate that variation of formation of 7-OH-MTX from MTX in vivo in rats is due primarily to variation of aldehyde oxidase.
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