Psychiatry related information on CCRIS 7628

• Plasma ratios of trans-3'-hydroxycotinine (3HC) to cotinine (COT) were examined in 92 cessation treatment-seeking adolescents (mean age 15.2 years, standard deviation [SD] 1.3, 69% female, 31% African American, mean Fagerström Test for Nicotine Dependence [FTND] 6.5, SD 1.6, mean years smoked 2.6, SD 1.6) [1].

High impact information on CCRIS 7628

• Our objective was to evaluate the use of oral nicotine with measurement of the trans-3'-hydroxycotinine (3HC)/cotinine (COT) metabolite ratio as a noninvasive probe of CYP2A6 activity [2].
• N-glucuronidation of trans-3'-hydroxycotinine by human liver microsomes [3].
• Nicotine and it chief metabolites, cotinine and trans-3'-hydroxycotinine were measured in the urine and adjusted for pH [4].
• We studied the formation of trans-3'-hydroxycotinine from cotinine in human liver microsomes. trans-3'-Hydroxycotinine formation demonstrated single enzyme Michaelis-Menten kinetics (Km, 234.5 +/- 26.8 MicroM; Vmax, 37.2 +/- 2.4 pmol/min/mg protein) [5].
• 4-Carboxyl-substituted analogues of trans-3'-hydroxycotinine were synthesized to be covalently linked to macromolecules for antibody production [6].

Biological context of CCRIS 7628

• The conjugated trans-3'-hydroxycotinine was determined after enzymatic hydrolysis [7].
• This study also validates a recently proposed method for estimating absolute bioavailability of a drug using drug and metabolite pharmacokinetic data, and presents novel data on plasma levels of the metabolite trans-3'-hydroxycotinine in people [8].

Anatomical context of CCRIS 7628

• Nicotine, cotinine, and trans-3-hydroxycotinine levels in seminal plasma of smokers: effects on sperm parameters [9].
• In this study, we measured the excretion rate of nicotine and its two major metabolites, cotinine and trans-3'-hydroxycotinine (THOC), in the urine of 25 healthy smokers and 15 smokers who underwent a coronary artery bypass surgery or coronary angioplasty [10].
• No evidence for a mutagenic activity of 3'-hydroxycotinine or of urine extracts from subjects dosed with hydroxycotinine was found with the S. typhimurium (TA 98) microsome assay [11].

Associations of CCRIS 7628 with other chemical compounds

• Synthesis of a hapten to be used in development of immunoassays for trans-3'-hydroxycotinine, a major metabolite of cotinine [6].
• Incubation of human liver microsomes with UDP-glucuronic acid produces not only trans-3'-hydroxycotinine O-glucuronide but also N-glucuronide [12].
• This method proved to be robust and accurate for the quantification of nicotine, cotinine, trans-3'-hydroxycotinine, and norcotinine in human plasma collected in clinical studies of acute nicotine effects on brain activity and on the development of neonates of maternal smokers [13].
• Interestingly, imipramine (IC(50) = 45 microM), androstanediol (IC(50) = 21 microM), and propofol (IC(50) = 41 microM) also inhibited trans-3'-hydroxycotinine O-glucuronosyltransferase activity by recombinant UGT2B7 [12].

Gene context of CCRIS 7628

• Trans-3'-hydroxycotinine O-glucuronosyltransferase activity by recombinant UGT2B7 increased with an increase in the substrate concentration up to 16 mM (10.5 pmol/min/mg) [12].
• Recombinant UGT1A4 exhibited substantial trans-3'-hydroxycotinine N-glucuronosyltransferase activity [12].
• These findings suggested that trans-3'-hydroxycotinine O-glucuronidation in human liver microsomes is catalyzed by mainly UGT2B7 and, to a minor extent, by UGT1A9 [12].
• CYP2A13 also catalyzes the 3'-hydroxylation of cotinine to form trans-3'-hydroxycotinine, with the apparent K(m) and V(max) values of 45.2 microM and 0.7 pmol/min/pmol, respectively [14].

Analytical, diagnostic and therapeutic context of CCRIS 7628

• Determination of the nicotine metabolite trans-3'-hydroxycotinine in urine of smokers using gas chromatography with nitrogen-selective detection or selected ion monitoring [15].
• An HPLC method was employed to determine simultaneously nicotine, cotinine and trans-3'-hydroxycotinine in the children's urine [16].
• A high-performance liquid chromatography (HPLC) method was used to determine urinary nicotine and its metabolites, cotinine and trans-3'-hydroxycotinine (OH-cotinine) to objectivise prenatal smoke exposure [17].
• After oral administration of 30 mg trans-3'-hydroxycotinine, the cumulative excretion rates of two subjects were 81% and 93% of the unchanged compound, respectively [18].

References