Cytochromes P450 tissue distribution

Wu, M. L., Wu, X. H. Chen, S. C. (2005). Study on tissue distribution difference of cytochrome P450 2C19 in Chinese population Han. Journal of Chinese Pharmaceuticals, 40(3), 215-18. 

Wacher, V. J., Wu, C. Y., Benet, L. Z., Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein implications for drug delivery and activity in cancer chemotherapy, Mol. Carcinogen. 1995, 13, 129-134. 

The CNS contains much smaller amounts of drug-metabolizing enzymes than does the liver. The concentrations of the main enzymes in the brain, members of the cytochrome P450 (CYP) superfamily, are only 0.25% of concentration in the liver. But the brain enzymes are not uniformly distributed, as they are in the liver they are concentrated in specific brain areas. Theoretical models have explained that drug metabolism in the CNS cannot influence drug distribution in the blood, but there are marked differences in brain tissue levels depending on the presence... 

Wacher VJ, Wu CY and Benet LZ (1995) Overlapping Substrate Specificities and Tissue Distribution of Cytochrome-P450 3a and P-Glycoprotein—Implications for Drug-Delivery and Activity in Cancer-Chemotherapy. Mol Carcinog 13 pp 129-134. 

Nishimura M, Yaguti H, Yoshitsugu H, Naito S, Satoh T (2003) Tissue distribution of mRNA expression of human cytochrome P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi 123(5) 369-375. 

Karlgren M, Backlund M, Johansson I, Oscarson M, Ingelman-Sundberg M. 2004. Characterization and tissue distribution of a novel human cytochrome P450-CYP2U1. Biochem Biophys Res Commun 315 679-685. 

Some specific molecules that are important in protein-drug interactions have been studied extensively, including cytochrome P450 (CYP450), receptors, membrane transporters, and antibodies (see Table 1.6). Databases about these molecules may also contain information about SNP effects, tissue distribution, and interacting substrates. 

Rylander, T., Neve, E. P, Ingelman-Sundberg, M., and Oscarson, M. Identification and tissue distribution of the novel human cytochrome P450 2S1 (CYP2S1). Biochem. Biophys. Res. Commun. 281(2) 529-535, 2001. 

Yamamoto Y, Ishizuka M, Takada A, et al. Cloning, tissue distribution, and functional expression of two novel rabbit cytochrome P450 isozymes, CYP2D23 and CYP2D24. J Biochem 1998 124 503-508. 

The relatively high affinity of these chemicals for lipid-rich tissues (Lipniak and Brandys, 1993) leads to disposition of B(a)P in rodent brain regions (Das et al, 1985). The intra-regional distribution of cytochrome P450 in brain tissues contributes to quantitative differences in PAH metabolite levels (Saunders et al, 2002 Brown et al, 2007). Several... 

Ketoconazole is well absorbed from the gut (poorly where there is gastric hypoacidity, see below) it is widely distributed in tissues but concentrations in CSF and urine are low its action is terminated by metabolism by cytochrome P450 3A (CYP 3A) (t) 8 h). Ketoconazole is effective by mouth for systemic mycoses (see Table 14.2) but has been superseded by fluconazole and itraconazole for many indications largely on groimds of improved pharmacokinetics, imwanted effect profile and efficacy. Impairment of steroid synthesis by ketoconazole has been put to other uses, e.g. inhibition of testosterone synthesis lessens bone pain in patients with advanced androgen-dependent prostatic cancer. 

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