4.4 Article

Estimation of aldehyde oxidase activity in vivo from conversion ratio of N1-methylnicotinamide to pyridones, and intraspecies variation of the enzyme activity in rats

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DRUG METABOLISM AND DISPOSITION
卷 34, 期 2, 页码 208-212

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AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/dmd.105.006544

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The in vivo conversion ratio of N-1-methylnicotinamide (NMN) to N-1-methyl-2-pyridone-5-carboxamide (2-PY) and N-1-methyl-4-pyridone-3-carboxamide (4-PY) as a parameter for the estimation of aldehyde oxidase level in rats was examined. NMN and its pyridones (2-PY and 4-PY) are usually detected in the urine of rats. When we measured the ratio of the amount of pyridones to the total amount of NMN and pyridones (RP value) in the urine of rats, marked intraspecies variations were observed. The variation in RP value among strains was closely related to the differences of liver aldehyde oxidase activity measured with NMN as a substrate. RP values after administration of NMN to different strains of rats confirmed the existence of strain differences of aldehyde oxidase activity in vivo. We demonstrated that measurements of NMN and its pyridones usually excreted in the urine can be used to predict the in vivo level of aldehyde oxidase.

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