Drug Metabolism in Drug Design and Development Basic Concepts and Practice

purified enzyme systems to multienzyme (i.e., microsomes or hepatocytes) systems. To utilize this approach, a standard probe sub ...

for the calculation of the RAF value(s) particularly for enzymes that demonstrate substrate dependent kinetic relationships (i.e ...

15.7.1 QuantitativeIn vitroRadiolabeled Reaction Phenotyping Studies Experimental methodologies utilizing radiolabeled compound ...

accurately reflect the true metabolic profile of the compound and may reflect experimental or analytical issues (i.e., the radio ...

The pharmacokinetic and metabolic evaluation of a single oral and IV dose of sildenafil (see Section 15.6.4.4 forin vitroreactio ...

is important when making projections to keep in mind the overall contribution of an enzyme. For example, expressed P450 enzyme a ...

15.7.4 Specialized Clinical Studies Clinical studies may be conducted to further evaluate the impact of metabolism via a polymor ...

References Abell CW, Kwan SW. Molecular characterization of monoamine oxidases A and B. Prog Nucleic Acid Res Mol Biol 2001;65:1 ...

Draganov DI, La Du BN. Pharmacogenetics of paraoxonases: a brief review. Naunyn- Schmiedebergs Arch Pharmacol 2004;369:78–88. Ed ...

between Japanese and Caucasian livers using rizatriptan, a serotonin receptor 1B/1D agonist, as a model drug. Br J Clin Pharmaco ...

Obach RS, Reed-Hagen AE. Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a sub ...

drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 199 ...

drugs fromin vitrodata: the effect of fluconazole on zidovudine glucuronidation. Br J Clin Pharmacol. Forthcoming. Venkatakrishn ...

APPENDIX A: REACTION PHENOTYPINGEXPRESSED cDNA ENZYME INCUBATION METHOD SHEET I. Objective A. To determine whether individuall ...

APPENDIX B: REACTION PHENOTYPING—MICROSOMAL CHEMICAL INHIBITION I. Objective A. To specifically inhibit CYP450s in human liver m ...

16 ANALYSIS OF IN VITRO CYTOCHROME P450 INHIBITION IN DRUG DISCOVERY AND DEVELOPMENT MAGANGSHOU ANDRENKEDAI 16.1 INTRODUCTION In ...

Thummel and Wilkinson 1998). The majority of drug interactions of clinical significance have occurred through interactions at th ...

Radioisotope-based inhibition assays have been also developed for the CYP inhibition using probe substrates, in which the O- or ...

16.2.1 Materials and Reagents Chemicals available from the commercial sources below: phenacetin, acetaminophen, diclofenac, cort ...

transfer, dilution, and incubation. Gemini software version 4.0 was used for programming the operation. A general instruction of ...