Identification of phenobarbital N-glucuronides as urinary metabolites of phenobarbital in mice

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298-0540, USA.
Drug Metabolism and Disposition (Impact Factor: 3.25). 06/1995; 23(5):548-52.
Source: PubMed


Mice were evaluated for their ability to form phenobarbital N-glucuronides. Following oral administration of [14C]phenobarbital to mice, a radiolabeled phenobarbital metabolite cochromatographed with synthetic standards of phenobarbital N-glucuronides. The phenobarbital N-glucuronides were partially purified from the mouse urine as phenobarbital N-methylglucuronates. The phenobarbital N-methylglucuronates isolated from mouse urine had similar chromatographic and spectroscopic properties as synthetic standards. The diastereomers of phenobarbital N-glucuronides and phenobarbital N-glucosides accounted for 7.8 +/- 2.3% and 1.6 +/- 0.6%, respectively, of the radioactivity excreted in mouse urine in the first 48 hr after dosing. This study indicates that the mouse may be a suitable species to study both N-glucosidation and N-glucuronidation simultaneously as metabolic pathways for barbiturates.

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    • "Regarding the metabolism of barbiturate derivatives, the N-glucoside forms of phenobarbital [5] and amobarbital [6] are known as the main metabolites in humans, but no Nglucuronide forms of these compounds have been confirmed . Neighbors et al. [7] reported the presence of Nglucuronide and N-glucoside in urine of mice treated with phenobarbital, and Mohri et al. [8] reported the "
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