Abstract
The metabolism of N-n-butyl barbital (nBB) in the rat was determined using the 14C-and 14C,15N-labeled compound. The metabolites formed in vivo and by the postmitochondrial fraction of liver were characterized and identified by gas chromatography-mass spectrometry, countercurrent distribution, partition coefficients, pK and Rf values. Rats given 14C-nBB (37 mg/kg i.v.) excreted 70 to 90% of the 14C in the urine and 19 to 7% in the feces. Of the 14C excreted in the urine, 70% was identified as a conjugate of N-(3-hydroxy-n-butyl)-barbital (3'-OH-nBB), 13% as N-(2,3-dihydroxy-n-buntyl)-bar-bital and 3% as 3'-OH-nBB. When 14C, 15N-nBB was incubated with the 9000 x g supernatant from liver, 80% of the total metabolite formed after 60 minutes was identified as 3'-OH-nBB, 6% as N-(3-keto-n-buntyl)-barbital and 4% as N-(2-hydroxy-n-butyl)-barbital (2'-OH-nBB). Pretreatment of rats with phenobarbital, 80 mg/kg/day for 4 days, caused a 5-fold increase in the rate of metabolism and drastically altered the ratio of 3'-OH-nBB to 2'-OH-nBB. Thus, after 60 minutes incubation, 47% of the total metabolite formed was identified as 3'-OH-nBB and 30% as 2'-OH-nBB.
Footnotes
- Received January 14, 1974.
- Accepted April 23, 1974.
- © 1974 by The Williams & Wilkins Co.
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