Cytochrome P450 time-dependent

McGinnity, D.F., Berry, A.J., Kenny J.R., Grime, K. and Riley, R.J. (2006) Evaluation of time-dependent cytochrome P450 inhibition using cultured human hepatocytes. Drug Metabolism and Disposition, 34 (8), 1291-1300. 

Atkinson, A., Kenny, J.R. and Grime, K. (2005) Automated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis. Drug Metabolism and Disposition, 33 (11), 1637—1647. 

Pharmacokinetic (PK) studies in different animal species and additional in vitro studies provide information on the compound s predicted human PK parameters, including dose- and time-dependencies, its protein binding, the effect of food on its PK, and the cytochrome P450 isoenzymes responsible for its metabolism as well as the stmcture and activity of the main metabolites. Also a sensitive assay to quantify the compound and its metabolites in human blood and urine should have been developed and validated. 

Santostefano MJ, Wang X, Richardson VM, et al. 1998. A pharmacodynamic analysis of TCDD-induced cytochrome P450 gene expression in multiple tissues dose- and time-dependent effects. ToxAppl Pharmacol 151 294-310. 

Figure 13 Dose- and time-dependent induction of CYP3A4 (A), CYP3A5 (B), and CYP3A7 (C) mRNAs in human cultured hepatocytes incubated with rifampicin. Cells cultured on Matrigel-coated 96-well plates were incubated with increasing doses of rifampicin, and RNA was harvested at times indicated. Specific CYP mRNAs were determined by TaqMan RT-PCR. Abbreviations. CYP, cytochrome P450 RT-PCR, realtime reverse transcriptase-polymerase chain reaction.

Peters WHM, Reolofs HMJ (1989) Time-dependent activity and expression of glutathion-S-transferases in the human adenocarcinoma cell line CACO-2. Biochem J 264 613-616 Rosenberg DW, Leff T (1993) Regulation of cytochrom P450 in cultured human colonic cells. Arch Biochem Biophys 300 186-192... 

During periods of immune system response, for example, at times of infectious disease, cytochrome P450-dependent metabolism of xenobiotics is reduced. This effect is attributed to the production of interferon by the immune system as it responds to a challenge. Human interferon has been shown to suppress the metabolism of benzo [a] pyrene in laboratory animalsJ19 ... 

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