Drug Metabolism in Drug Design and Development Basic Concepts and Practice

day when the measurement of radioactivity in excreta is1% of administered radioactivity. 18.2.3 Dose Selection, Formulation, an ...

higher volumes (such as ethanol, cremophor), that is substituted with water, saline, buffer, etc. In human ADME studies, general ...

0,0.25,0.5,1,2,4,6,8,12,24,48,72,96,120,144,and168hpostdosefor PK analysis. 18.2.4.3 Human Blood (10 mL) for at least four time ...

18.3.1.1 Plasma The plasma sample is treated with an organic solvent such as acetonitrile, methanol or methanol/acetonitrile (1 ...

blood, and tissues for 24–48 h at room temperature with Soluene-350 (Packard Instrument Co., Meriden, CT). The digested aliquots ...

analyzed by a noncompartmental method (Gibaldi and Perrier, 1982). The peak plasma concentration,Cmax, and the time to reach pea ...

profiles are reported as a percentage of the total radioactivity collected during the entire HPLC run. The relative distribution ...

LC/MS/MS methods will often leave significant ambiguity in the exact structural identification of metabolites. The next level of ...

extracts were analyzed by LC/MS. For metabolite isolation, fractions were collected from multiple injections (100mL) onto a HPLC ...

dose is readily excreted from the body. The amount of radioactivity is usually expressed as the percent of the dose in each matr ...

In addition to determine the major metabolic pathways of a drug, the radioactivity and the unchanged drug concentration in blood ...

0 2 4 6 8 10 12 14 0 10 20 30 40 50 60 70 80 Rat Dog Monkey Human Total radioactivity ( mg muraglitazar equivalent/g) Plasma c ...

0 500 1000 1500 2000 0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 0 25 50 75 100 0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.0 ...

18.4.2 Metabolite Profiles in Plasma, Urine, Bile, and Feces In order to determine the metabolic fate of a radiolabeled drug, ra ...

18.4.2.2 Urine The HPLC radiochromatographic profiles of pooled urine from rats, dogs, monkeys, and humans were also determined ...

P P 13 13 15 15 20 20 18a,b,c 10 11 21 1 6 2 4 5 17a,b,c HPLC time (min) CPM Monkey 0 200 400 600 800 1000 0.00 10.00 20.00 30.0 ...

18.4.2.4 Summary of Metabolite Profiling Parent compound was the major circulating, drug-related component in rats, dogs, monkey ...

O-demethylation.^1 Hand^13 CNMR analyses showed that M15 lacked the OCH 3 group (at 3.8 ppm for^1 Hand 55 ppm for^13 C) observed ...

TABLE 18.8 Structures of muraglitazar and its metabolites (M1, M2, M4, M4, M5). Drug or metabolite Proposed structurea Source Mu ...

to be qualified. MDF-treated ion chromatograms may have provided the first useful LC/MS method for estimation of amounts of meta ...