Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 17.1 CYP isoform-specific inducers and substrates used in in vitro models. CYP Preferred inducer ( m M) Acceptable inducer ...

PXR, in the presence of a CYP3A4 inducer, binds to and activates the responsive elements in a reporter gene construct, leading t ...

as follows: For the PXR expression vector, a full-length PXR open reading frame was amplified by RT–PCR from human liver RNA usi ...

TABLE 17.2 Summary of Human PXR reporter gene assays used in several laboratories.Author PXR Construct Reporter gene construct C ...

A eukaryotic expression vector such as pSG5 (Stratagene) or pCMV (Promega), with a human PXR open reading frame cDNA insert, is ...

these methods do not directly assess the potential of a compound to induce CYP3A4 in humans under clinical conditions. The predi ...

found that rifampicin significantly enhanced the total body clearance of midazolam, from 5.5 mL/min/kg on day 1 to 10.1 mL/min/k ...

which may not affect the results of thein vitroscreening assays, but may have a major effect on the effective concentration of t ...

transporter proteins such as Pgp, MRP2, and OATP (Eloranta et al., 2005; Klaassen and Slitt, 2005). When CYP3A4 induction occurs ...

Desai PB, Nallani SC, Sane RS, Moore LB, Goodwin BJ, Buckley DJ, Buckley AR. Induction of cytochrome P450 3A4 in primary human h ...

Jones SA, Moore LB, Shenk JL, Wisely GB, Hamilton GA, McKee DD, Tomkinson NC, LeCluyse EL, Lambert MH, Willson TM, Kliewer SA, M ...

hepatocytes from man, Sprague–Dawley rat, minipig, and beagle dog. Chem Biol Interact 2001;134:271–281. Luo G, Cunningham M, Kim ...

Okey AB, Riddick DS, Harper PA. Molecular biology of the aromatic hydrocarbon (dioxin) receptor. Trends Pharmacol Sci 1994;15:22 ...

Sueyoshi T, Negishi M. Phenobarbital response elements of cytochrome P450 genes and nuclear receptors. Annu Rev Pharmacol Toxico ...

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18 ADME STUDIES IN ANIMALS AND HUMANS: EXPERIMENTAL DESIGN, METABOLITE PROFILING AND IDENTIFICATION, AND DATA PRESENTATION DONGL ...

major clearance pathways. The ADME data will also define relative concentra- tions of each metabolite in plasma, urine, bile, an ...

radiolabeled compound are often conducted in preclinical and early clinical stages, especially when a toxic dose and the therape ...

be acceptable. Radiopurity of the radiolabeled drug should be checked before dose preparation and stability (radiopurity) of the ...

fasted for 4 h, and rats, dogs, and monkeys are fasted overnight before dose administration. In general, a total of six to eight ...