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The synthesis of a novel gut selective MTP inhibitor, 5-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), and its in vitro and in vivo profile are described. Dirlotapide (3) demonstrated excellent potency against MTP enzyme in HepG2 cells and canine hepatocytes. This novel MTP inhibitor(More)
3,3',4,4'-Tetrachloroazobenzene (TCAB) is a contaminant generated during the synthesis of 3,4-dichloroaniline and 3,4-dichloroaniline-derived pesticides. TCAB is isosteric to 2,3,7,8-tetrachlorodibenzo-p-dioxin and has been shown to bind to the Ah receptor. Following oral administration of [14C]TCAB (3.2 and 32 mg/kg), 39-45% of the dosed radioactivity was(More)
An assay was developed for the simultaneous measurement of cyclohexene oxide and its metabolites (cyclohexanol, trans-cyclohexane-1,2-diol, cyclohexane-1,2-diol-O-glucuronide, and N-acetyl-S-(2-hydroxycyclohexyl)-L-cysteine) in rat urine and plasma using gas chromatography. A mixture of ethyl acetate-acetonitrile (70:30) was used as the extracting solvent(More)
Cyclohexene oxide (CHO) is a monomer intermediate used in the synthesis of pesticides, pharmaceuticals, and perfumes. Although CHO has a variety of industrial uses where direct human exposure is possible, very little is known about its fate in the body. Therefore, the objectives of this study were to determine the absorption, distribution, metabolism, and(More)
Few studies are available characterizing the effects of fibrosis on pulmonary disposition of drugs or environmental pollutants. Two model substrates, p-nitroanisole and carbofuran, were selected to evaluate the effect of bleomycin-induced fibrosis on pulmonary disposition and metabolism using the isolated perfused lung and in vitro enzyme preparations. The(More)
The effects of two representative sulfonylureas, tolbutamide and glyburide, on pyruvate kinase (PK) flux were examined in fasted rat hepatocytes. PK flux was estimated by trapping 14C from NaH14CO3 in a 2 mM lactate pool, accounting for any incomplete trapping by parallel incubations with L-[1-14C]alanine. Glyburide (20 microM) and tolbutamide (1 mM)(More)
3,3',4,4'-Tetrachloroazoxybenzene (TCAOB) is a structural analog of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It is formed as a byproduct during the synthesis of industrial products such as herbicides. TCAOB is a ligand for the Ah receptor and, at much higher doses, exhibits toxicities similar to TCDD. Although the reduced in vivo toxicity of TCAOB(More)
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