PMID: 6111434Jan 1, 1981Paper

Stereoselective formation of glucuronides in metabolism of hexobarbital enantiomers in vivo: isolation and quantitation of glucuronides in rabbit urine

Drug Metabolism and Disposition : the Biological Fate of Chemicals
K MiyanoS Toki

Abstract

An improved column-chromatographic method was described for isolation and purification on preparative scale of a glucuronide from urine of rabbits administered (RS)-hexobarbital. The analytically pure preparation obtained was found to be a mixture of two glucuronides of diastereomeric 3'-hydroxyhexobarbitals. Rates of hydrolysis of the glucuronides were dependent on the enzyme preparations used as well as on the configuration of the substrate. For quantitative determination, the glucuronides were hydrolyzed completely by beta-glucuronidases from either Escherichia coli or abalone entrails under the conditions used. In vivo studies on the metabolism of (R)-(-)- and (S)-(+)-hexobarbital in the rabbit showed that the glucuronides excreted in 24-hr urine accounted for about 30% of the dose of each enantiomer, and that conjugation of the hydroxy isomers with glucuronic acid was so stereoselective that the isomers with S-configuration at the 3'-position were preferentially conjugated. There were almost no differences in the urinary metabolite profile between normal an PB-treated rabbits; however, a noticeable change was observed in recovery of unchanged (S)-hexobarbital after phenobarbital treatment.

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.