Drug Metabolism in Drug Design and Development Basic Concepts and Practice

compound and its metabolites.R-(+)-Pulegone is used as a positive control. (4) Add 10mL of the NADPH stock solution to start the ...

pair of 340 and 525 nm. The final quantitative result of dGSH adduct formation is expressed as percentage of initial compound co ...

14.1.5 Notes (1) Investigators may use a mixture of GSH and its stable labeled analog (L-g-glutamyl-L-cysteinyl-glycine-^13 C 2 ...

(3) In some cases, bis-adducts may be formed in trapping studies. It is recommended to extract MS spectra of these potential add ...

protein binding studies, particularly when such a possibility is obvious theoretically. Alternative radiolabeled tracers should ...

was reported that the covalent protein binding values of reference model compounds in human and rat liver microsomes were136 an ...

radioactivity. The second portion (0.5 mL) of the last eluate is evaporated to dryness under nitrogen overnight. The residue is ...

duplicate is taken for protein assays using the BCA method. The remaining sample in each vial is then mixed with 5 mL of scintil ...

protein is estimated based on the residual radioactivity in the proteins. An example of covalent protein binding studies in live ...

(4) If^14 C-tracers are used inin vivocovalent protein binding studies in rats, evaluation of the loss of the^14 C-label in rat ...

radical generated from above redox cycling of quinones can oxidize cysteine residues of proteins, causing oxidative stress in ce ...

Chemically, GSH can also be derivatized by iodoacetamide (IAM, Fig. 14.1) to form the corresponding GS–AM conjugate. The followi ...

quaternary pump and a Series 200 autosampler (Norwark, CT). The mass spectrometer employs an electrospray ionization probe with ...

P450 inhibitors (Bateman et al., 2004; Blobaum et al., 2002; Correia and Ortiz de Montellano, 2005; Koenigs et al., 1999). A pot ...

may contribute to formation of the potentially toxic covalent zomepirac– protein adductsin vitroin rat hepatocytes andin vivoin ...

Bolton JL, Trush MA, Penning TM, Dryhurst G, Monks TJ. Role of quinones in toxicity. Chem Res Toxicol 2000;13:135–160. Bolze S, ...

Guengerich FP. Metabolic activation of carcinogens. Pharmacol Ther 1992;54:17–61. Guengerich FP. Common and uncommon cytochrome ...

Park BK, Kitteringham NR, Maggs JL, Pirmohamed M, Williams DP. The role of metabolic activation in drug-induced hepatotoxicity. ...

Ward D, Kalir A, Trevor A, Adams J, Baillie T, Castagnoli N. Metabolic formation of iminium species: the metabolism of phencycli ...

15 Reaction Phenotyping SUSANHURST,J.ANDREWWILLIAMS,ANDSTEVENHANSEL 15.1 INTRODUCTION Consistent, predictable efficacy, and safe ...