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Differences in the absorption, metabolism and biliary excretion of a diastereomeric pair of alphavbeta3-antagonists in rat: limited role of ...
I exhibited a higher metabolic clearance (>2-fold higher than II), whereas the hydrophilic zwitterion II exhibited a higher biliary clearance (approximately 5-fold higher than I). Following oral administration, the bioavailability (F) of I (17%) was much higher than that of II (1%). 3. Consistent wi...
Metabolic inactivation of 2-oxiranylmethyl 2-ethyl-2,5-dimethylhexanoate (C10GE) in skin, lung and liver of human, rat and mouse.
The inactivation of 2-oxiranylmethyl 2-ethyl-2,5-dimethylhexanoate (C10GE), one of the most abundant isomers of the epoxy-resin Carduras E-10 glycidyl ester, was studied in subcellular fractions of human, C3H mouse and F344 rat liver, lung and skin. C10GE is chemically very stable and resistant to a...
Urinary metabolites of a novel quinoxaline non-nucleoside reverse transcriptase inhibitor in dog, cynomolgus monkey and mini-pig.
1. The metabolism of (S)-2-ethyl-7-fluoro-3-oxo-3,4-dihydro-2H-quinoxalinecarboxylic acid isopropylester (GW420867X) has been investigated following oral administration to dog, cynomolgus monkey and mini-pig. 2. The urinary metabolites were isolated and characterized using semi-preparative HPLC, NMR...
Inhibition and induction of human cytochrome P450 (CYP) enzymes.
Metabolism of a novel CCK-B antagonist in rat, dog and human liver microsomes.
1. The in vitro metabolism of a novel CCK-B antagonist ((+)-N-[1-adamantane-1-methyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H- 1, 5-benzodiazepin-3-yl]N'-phenyl-urea; GV150013X) was investigated using rat, dog and human liver microsomes. 2. Four monohydroxy and four dihydroxy metabo...
Nuclear magnetic resonance timecourse studies of glyphosate metabolism by microbial soil isolates.
1. Triple Resonance Isotope EDited nmr spectroscopy (TRIED) has been developed to detect and examine minute levels of glyphosate metabolites in microbial soil isolates. Using stable isotopic labelling (13C and 15N), TRIED allows the simultaneous detection of multiple metabolites in crude matrices at...
Diethanolamine absorption, metabolism and disposition in rat and mouse following oral, intravenous and dermal administration.
1. The disposition of [14C]diethanolamine (DEA) (1) was determined in rat after oral, i.v. and dermal administration, and in mouse after dermal administration. 2. Oral administration of DEA to rat was by gavage of 7 mg/kg doses once and after daily repeat dosing for up to 8 weeks. Oral doses were we...
Are free radicals involved in lead poisoning?
1. The enolamine form of 5-aminolaevulinic acid (ALA), a haem precursor that accumulates in lead poisoning and in acute intermittent porphyria (AIP), undergoes fast autoxidation at slightly alkaline pH with concomitant generation of reactive oxygen species. 2. The transmembrane potential, Ca2+ ion f...
Metabolism of inhaled styrene in acetone-, phenobarbital- and 3-methylcholanthrene-pretreated rats: stimulation and stereochemical effects b...
Our conclusions are that styrene metabolism in vivo in both autoinduced and induced by other foreign compounds, that cytochrome P450IIE1 induction has a major impact on styrene metabolism and that P450IIB1 induction yields an altered MA metabolite enantiomer ratio....
Propofol: assay and regional mass balance in the sheep.
1. Pharmacokinetic data for propofol, a new intravenous anaesthetic agent, indicate that there may be extensive extrahepatic clearance. This was investigated during intravenous infusions of propofol in adult merino ewes with chronic intravascular cannulae using a newly developed simple and rapid ass...