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A study of the rates and routes of excretion of 3-fluoro-(U- 14 C)aniline following intraperitoneal administration to male bile-cannulated rats by liquid scintillation counting (LSC) gave a total recovery of ∼ 90% in the 48 h following dosing, with the majority of the dose being excreted in the...
4-Oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid (4-methylaminomethyl-phenyl)-amide (1), developed for general anxiety disorder, was discontinued from clinical development due to unsuitable oral pharmacokinetics. In humans, (1) demonstrated an unacceptable high apparent oral clearance ( Cl p...
To analyze the polymorphic activities of CYP2C8 and evaluate their impact on drug inhibitory potential, three CYP2C8 allelic variants (CYP2C8.2, CYP2C8.3, and CYP2C8.4), two non-synonymous single nucleotide polymorphic variants (R139K and K399R, carried by CYP2C8.3), and wild-type CYP2C8...
The effect of flavonoids on coumarin 7-hydroxylation, an activity marker of an important human liver cytochrome P450 isoform, cytochrome P450 2A6 (CYP2A6), was investigated in this study. Coumarin 7-hydroxylase activity was measured fluorometrically in reaction mixtures containing cDNA-expressed...
Tissue distribution, metabolism, and disposition of oral (0.2–20 mg/kg) and intravenous (0.2 mg/kg) doses of (2- 14 C)dibromoacetonitrile (DBAN) were investigated in male rats and mice. ( 14 C)DBAN reacts rapidly with rat blood in vitro and binds covalently. Prior depletion of glutathione (GSH)...
Zinc acexamate (ZAC) is ionized to zinc and ϵ-acetamidocaproic acid (AACA). Thus, the pharmacokinetics and tissue distribution of zinc and AACA after intravenous (50 mg kg −1 ) and oral (100 mg kg −1 ) administration of ZAC were evaluated in rats. Also the pharmacokinetics of AACA after...
Cytochrome P450 1B1 (CYP1B1) is highly expressed in testis, but there is conflicting information regarding the inducibility of testicular CYP1B1 by aryl hydrocarbon receptor (AhR) agonists. To assess AhR-mediated regulation, testicular CYP1B1 expression was measured following treatment of adult...
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