Drugs cytochrome P450-mediated

Korolev D, Balakin KV, Nikolsky Y, Kirillov E, Ivanenkov YA, Savchuk NP, Ivashchenko A A, Nikolskaya T. Modeling of human cytochrome p450-mediated drug metabolism using unsupervised machine learning approach. J Med Chem 2003 46 3631-43. 

Chauret, N., Gauthier, A. and Nicoll-Griffth, D.A. (1998) Effect of common solvents on in vitro cytochrome P450 mediated metabolic activities in human liver microsomes. Drug Metabolism and Disposition The Biological Fate of Chemicals, 26, 1-4. 

CKD may alter nonrenal clearance of drugs as the result of changes in cytochrome P450-mediated metabolism in the hver and other organs. The clinical reductions in nonrenal clearance in CKD are generally proportional to the reductions in glomerular filtration rate (Table 77-1). 

Shou M, Lin Y, Lu P, Tang C, Mei Q, et al. 2001. Enzyme kinetics of cytochrome P450-mediated reactions. Curr Drug Metab 2 17. 

Korolev, D., Balakin, K.V., Nikolsky, Y., Kirillov, E., Ivanenkov, Y.A., Savchuk, N.P., Ivashchenko, A.A., and Nikolskaya, T. Modeling ofhuman cytochrome p450-mediated drug metabolism using unsupervised machine learning approach./. Med. Chem. 2003, 46, 3631-3643. 

Waller, C. L., Evans, M. V., and McKinney, J. D. (1996) Modeling the cytochrome P450-mediated metabolism of chlorinated volatile organic compounds. Drug Metab. Dispos. 24, 203-210. 

Isoniazid inhibits cytochrome P450 enzyme function and thus can interact with drugs that are subject to cytochrome P450 mediated metabolism like warfarin and the antiepileptic agents phenytoin and car-bamazepine. 

Pharmacokinetics II cytochrome P450-mediated drug interactions... 

Mirtazapine has been shown to reduce anxiety symptoms and sleep disturbances associated with depression, as early as 1 week after the start of treatment. Other advantages are minimal sexual dysfunction, minimal nausea, and once-daily dosing. In addition, mirtazapine is unlikely to be associated with cytochrome P450-mediated drug interactions. The disadvantages of mirtazapine are weight gain and prominent early sedation. 

Guo LQ, Taniguchi M, Chen QY, Baba K, Yamazoe Y. Inhibitory potential of herbal medicines on human cytochrome P450-mediated oxidation properties of umbelliferous or citrus crude drugs and their relative prescriptions. Jpn J Pharmacol 2001 85 399 8. 

Li, H.Y. et al. (2008) Considerations and recent advances in QSAR models for cytochrome P450-mediated drug metabolism prediction. 

Oxybutynin has a relatively low oral bioavailability (6%) due to an extensive first-past presystemic metabolism after administration [194], Indeed, the absence of intact oxybutynin in urine suggests that the major elimination pathway of this drug is hepatic metabolism [195]. The compound is readily converted to its stable toxic metabolite, iV-desethyloxybutynin by cytochrome P450-mediated oxidation [196], Following oral administration of oxybutynin, peak plasma concentrations are reached within 1 h. The short half-life of this drug (less than 2 h), when administered as a conventional oral formulation, necessitates multiple 5 mg daily dosing [197],... 

Bredberg E, Andersson TB, Frison L, et al. Ximelagatran, an oral direct thrombin inhibitor, has a low potential for cytochrome P450-mediated drug-drug interactions. Clin Pharmacokinet 2003 42 765-777. 

Delaforge M, Provost A, Perrin L, et al. Cytochrome P450-mediated oxidation of glucuronide derivatives example of estradiol-17P-glucuronide oxidation to 2-hydroxy-estradiol-17P-glucuronide by CYP 2C8. Drug Metab Dispos 2005 33 4664-73. 

Gan LS, Moseley MA, Khosla B, et al. CYP3A-like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells. Drug Metab Dispos 1996 24(3) 344-349. 

OF CYTOCHROMES P450-MEDIATED DRUG-DRUG INTERACTIONS THAT LEAD TO TOXICITIES... 

Vuppugalla R, Mehvar R (2004) Hepatic Disposition and Effects of Nitric Oxide Donors Rapid and Concentration-Dependent Reduction in the Cytochrome P450-Mediated Drug Metabolism in Isolated Perfused Rat Livers. J Pharmacol Exp Ther (in press)... 

Colburn DE, Giles FJ, Oladovich D, Smith JA. In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology 2004 9(3) 217-21. 

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