The DOI matches its Crossref record.
Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians
Abstract
Interindividual variations in the level and activity of cytochrome P-450 enzymes were investigated in the liver microsomes of 30 Japanese and 30 Caucasian patients. The P-450 enzymes used in this study included P-450 1A2, 2A6, 2B6, 2C, 2D6, 2E1 and 3A, and the monooxygenase activities determined were 13 typical P-450 substrates and 9 procarcinogens. Although the total P-450 content was higher in Caucasian (mean, 0.43 nmol/mg of protein) than in Japanese populations (mean, 0.26 nmol/mg of protein), the relative levels (percent of total P-450) of individual forms of P-450 determined immunochemically were not very different except that P-450 2A6 and 2B6 levels were higher in the Caucasians. About 70% of liver P-450 could be accounted for by P-450 1A2, 2A6, 2B6, 2C, 2D6, 2E1 and 3A proteins, and P-450 3A (about 30% of total P-450) and 2C (about 20%) enzymes were found to be the major forms. Considerable levels of P-450 1A2 (about 13%) and 2E1 (about 7%) could be determined, whereas the P-450 2A6 (about 4%), 2D6 (about 2%) and 2B6 (< 1%) were the minor P-450 forms. Differences in some of the P-450 1A2-, 2A6-, 2D6-, 2E1- and 3A4-dependent activities were observed in Japanese and Caucasian populations. No clear sex-related differences in individual P-450 contents and drug- and carcinogen-metabolizing activities were detected in 60 human samples, except that P-450 1A2-dependent activities were found to be higher in mean than in women in the Caucasian population only. A single neonate sample tended to be lower in P-450 1A2-, 2A6- and 2E1-dependent activities. In contrast to rat counterparts, we could not detect apparent developmental changes in P-450 content and activity in humans between 12 and 73 years old. Thus, the results presented in this study provide useful information for the study of drug biotransformation in humans and for the basis of drug toxicities, carcinogenesis and teratogenesis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“CYP3A4 is the most abundant CYP expressed in the adult liver [121,122]”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [122]
In the citing paper
“makes the major contribution to steroid metabolism.”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [122]
In the citing paper
“CYP3A4 is the most abundant P450 in the liver (∼30%) (Shimada et al., 1994) and predominantly, though not exclusively, catalyses the 6β-hydroxylation of T and the 16α- and 7α-hydroxylation of DHEA (Niwa et al., 2015).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Shimada et al., 1994
Citations
Cited by
Sorted by citations
Zanger, U. M., & Schwab, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.12.007 · Cited by 4,169
“Human CYP2A6 is mainly expressed in liver (Table 2), where mean expression levels corresponding to ~4% of the hepatic P450 pool were found by Western blot analysis (Shimada et al., 1994; Haberl et al., 2005)whilemass spectrometric studies foundmuch higher levels of ~50 pmol/mg (Ohtsuki et al.”
BackgroundInfluentialKuehl, P. M., Zhang, J., Lin, Y., Lamba, J. K., Assem, M., Schuetz, J. D., Watkins, P. B., Daly, A. K., Wrighton, S. A., Hall, S. D., et al. (2001) · Nature Genetics · doi:10.1038/86882 · Cited by 2,172
Metabolism and Disposition Kinetics of Nicotine
Hukkanen, J., Jacob, P., & Benowitz, N. L. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.1.3 · Cited by 1,583
“Significant gender differences have not been detected in the amount or activity of CYP2A6 in liver microsomes in several studies with a small number of samples (Pearce et al., 1992; Shimada et al., 1994; Bourrie et al., 1996; Chauret et al., 1997; Baker et al., 2001; Schmidt et al., 2001).”
BackgroundMartignoni, M., Groothuis, G. M. M., & de Kanter, R. (2006) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2.6.875 · Cited by 1,478
“CYP2C19 proteins are primarily located in the liver where they account for approximately 20% of total cytochrome P450 [15].”
BackgroundInfluentialCYTOCHROME P-450 3A4: Regulation and Role in Drug Metabolism
Guengerich, F. P. (1999) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.39.1.1 · Cited by 1,271
Self-citationKetamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms
Zanos, P., Moaddel, R., Morris, P. J., Riggs, L. M., Highland, J. N., Georgiou, P., Pereira, E. F. R., Albuquerque, E. X., Thomas, C. J., Zarate, C. A., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.015198 · Cited by 1,260
“, 2012) has been attributed, in part, to differences in the expression of P450 enzymes (Shimada et al., 1994; Hijazi and Boulieu, 2002).”
BackgroundGenetic contribution to variable human CYP3A-mediated metabolism
Lamba, J. K., Lin, Y. S., Schuetz, E. G., & Thummel, K. E. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00066-2 · Cited by 987
Generation of a Set of Simple, Interpretable ADMET Rules of Thumb
Gleeson, M. P. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm701122q · Cited by 996
Dresser, G. K., Spence, J. D., & Bailey, D. G. (2000) · Clinical Pharmacokinetics · doi:10.2165/00003088-200038010-00003 · Cited by 908
THE HUMAN INTESTINAL CYTOCHROME P450 “PIE”
Paine, M. F., Hart, H. L., Ludington, S. S., Haining, R. L., Rettie, A. E., & Zeldin, D. C. (2006) · Drug Metabolism and Disposition · doi:10.1124/dmd.105.008672 · Cited by 870
“Large interindividual variation was also observed, ranging from 20-(CYP2E1, CYP3A4) to >1000-fold (CYP2D6) (Shimada et al., 1994).”
BackgroundMethodInfluentialIN VITRO AND IN VIVO DRUG INTERACTIONS INVOLVING HUMAN CYP3A
Thummel, K. E., & Wilkinson, G. R. (1998) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.38.1.389 · Cited by 823
Inhibition and Induction of Cytochrome P450 and the Clinical Implications
Lin, J. H., & Lu, A. Y. H. (1998) · Clinical Pharmacokinetics · doi:10.2165/00003088-199835050-00003 · Cited by 827
“[9] An early reported interactions with phenobarbital also involved oral anticoagulants.”
BackgroundPolymorphism of human cytochrome P450 enzymes and its clinical impact
Zhou, S., Liu, J., & Chowbay, B. (2009) · Drug Metabolism Reviews · doi:10.1080/03602530902843483 · Cited by 857
“Alleles of CYP2B6, ethnic distribution, and effect on enzyme activity Expression of CYP2B6 has been shown to be highly variable among human liver samples (Lang et al., 2004a; Shimada et al., 1994).”
BackgroundResultInfluentialPharmacokinetics and drug metabolism in the elderly
Klotz, U. (2009) · Drug Metabolism Reviews · doi:10.1080/03602530902722679 · Cited by 826
“Likewise, the content and activities of various CYP450 enzymes in hepatic biopsy samples did not decline with age in the range of 10–85 years (Schmucker et al., 1990; Hunt et al., 1992; Shimada et al., 1994; Hubbard et al., 2008).”
BackgroundHuman P450 metabolism of warfarin
Kaminsky, L. S., & Zhang, Z. (1997) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(96)00140-4 · Cited by 798
Paine, M. F., Khalighi, M., Fisher, J. M., Shen, D. D., Kunze, K. L., Marsh, C. L., Perkins, J. D., & Thummel, K. E. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37149-6 · Cited by 790
Aging Biology and Geriatric Clinical Pharmacology
McLean, A. J., & Couteur, D. G. L. (2004) · Pharmacological Reviews · doi:10.1124/pr.56.2.4 · Cited by 771
“No relationship has been found between age and the activities and content of various cytochrome P450 enzymes determined from microsomal preparations from liver resection specimens (Shimada et al., 1994).”
BackgroundBertz, R., & Granneman, G. R. (1997) · Clinical Pharmacokinetics · doi:10.2165/00003088-199732030-00004 · Cited by 754
Hewitt, N. J., Gómez Lechón, M. J., Houston, J. B., Hallifax, D., Brown, H. S., Maurel, P., Kenna, J. G., Gustavsson, L., Lohmann, C., Skonberg, C., et al. (2007) · Drug Metabolism Reviews · doi:10.1080/03602530601093489 · Cited by 735
Guengerich, F. P. (1995) · Springer eBooks · doi:10.1007/978-1-4757-2391-5_14 · Cited by 732
Self-citationBessems, J. G. M., & Vermeulen, N. P. E. (2001) · Critical Reviews in Toxicology · doi:10.1080/20014091111677 · Cited by 716
“The major P450 enzymes in the Caucasian as well as the Japanese population are those of the CYP3A (about 30% of total P450) and CYP2C (about 20%) subfamily, followed by CYP1A2 (about 13%), CYP2E1 (about 7%), CYP2A6 (about 4%), CYP2D6 (about 2%) and CYP2B6 (< 1%) (Shimada et al., 1994).”
BackgroundRemoval of the hazardous dye rhodamine B through photocatalytic and adsorption treatments
Jain, R., Mathur, M., Sikarwar, S., & Mittal, A. (2007) · Journal of Environmental Management · doi:10.1016/j.jenvman.2006.11.002 · Cited by 715
Role of Pharmacokinetics and Metabolism in Drug Discovery and Development
Lin, J. H., & Lu, A. Y. H. (1997) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01340-1 · Cited by 713
“…et al. (1996) successfully predicted the in vivo clearance and bioavailability of YM796, a CNS drug for the treatment of Alzheimer’s disease, using a recombinant system of human CYP3A4 together with the information of the content of this isoform in human liver microsomes (Shimada et al., 1994).”
Yano, J. K., Wester, M. R., Schoch, G., Griffin, K. J., Stout, C. D., & Johnson, E. F. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400293200 · Cited by 705
Lown, K. S., Mayo, R. R., Leichtman, A. B., Hsiao, H.-L., Turgeon, D. K., Schmiedlin‐Ren, P., Brown, M. B., Guo, W.-S., Rossi, S. J., Benet, L. Z., et al. (1997) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(97)90027-8 · Cited by 679
The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism
Wei, P., Zhang, J., Egan-Hafley, M., Liang, S., & Moore, D. D. (2000) · Nature · doi:10.1038/35038112 · Cited by 654
Pregnancy-Induced Changes in Pharmacokinetics
Anderson, G. D. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544100-00001 · Cited by 650
Haas, D. W., Ribaudo, H. J., Kim, R. B., et al. (2004) · PubMed · Cited by 628
Lown, K. S., Bailey, D. G., Fontana, R. J., Janardan, S. K., Adair, C. H., Fortlage, L. A., Brown, M. B., Guo, W., & Watkins, P. B. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119439 · Cited by 624
“) CYP3A4 is the most abundant cytochrome P450 present in both the liver (18) and in the epithelial cells (enterocytes) that line the lumen of the small bowel (19, 20).”
BackgroundShimada, T. (2006) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.21.257 · Cited by 606
Self-citationMolecular Basis of Ethnic Differences in Drug Disposition and Response
Xie, H., Kim, R. B., Wood, A. J. J., & Stein, C. M. (2001) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.815 · Cited by 600
“CYP3A4 is abundantly present in human liver and small intestine (15, 136) and contributes to the metabolism of ∼50% of commonly used drugs including nifedipine, cyclosporine, erythromycin, midazolam, alprazolam, and triazolam (136–141).”
BackgroundMethodInfluentialWard, B. A., Gorski, J. C., Jones, D. R., Hall, S. D., Flockhart, D. A., & Desta, Z. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.049601 · Cited by 593
“It is now believed that 8% of the drugs on the market are fully or partially metabolized by CYP2B6 (Treger and Stoll, 2002), and it represents 6% of the total liver P450 content (Stresser and Kupfer, 1999), in contrast to earlier estimates that it represented less than 1% (Shimada et al., 1994).”
Resultde Wildt, S. N., Kearns, G. L., Leeder, J. S., & van den Anker, J. N. (1999) · Clinical Pharmacokinetics · doi:10.2165/00003088-199937060-00004 · Cited by 590
Lang, T., Klein, K., Fischer, J., Nussler, A. K., Neuhaus, P., Hofmann, U., Eichelbaum, M., Schwab, M. G., & Zanger, U. M. (2001) · Pharmacogenetics · doi:10.1097/00008571-200107000-00004 · Cited by 571
Coumarin Metabolism, Toxicity and Carcinogenicity: Relevance for Human Risk Assessment
Lake, B. G. (1999) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(99)00010-1 · Cited by 562
Lacroix, D. A., Sonnier, M., Moncion, A., Chéron, G., & Cresteil, T. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00625.x · Cited by 537
Sex Differences in Pharmacokinetics and Pharmacodynamics
Gandhi, M., Aweeka, F. T., Greenblatt, R. M., & Blaschke, T. F. (2004) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.44.101802.121453 · Cited by 546
The Gut as a Barrier to Drug Absorption
Zhang, Y., & Benet, L. Z. (2001) · Clinical Pharmacokinetics · doi:10.2165/00003088-200140030-00002 · Cited by 521
“[28-30] Among the CYP3A subfamily, CYP3A4 is the most abundant andmost important enzyme in human drug metabolism.”
BackgroundMechanism-Based Inhibition of Cytochrome P450 3A4 by Therapeutic Drugs
Zhou, S., Chan, S. Y., Goh, B. C., Chan, E., Duan, W., Huang, M., & McLeod, H. L. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544030-00005 · Cited by 512
Sex Is A Major Determinant of Cyp3a4 Expression in Human Liver
Wolbold, R., Klein, K., Burk, O., Nussler, A. K., Neuhaus, P., Eichelbaum, M. F., Schwab, M. G., & Zanger, U. M. (2003) · Hepatology · doi:10.1002/hep.1840380424 · Cited by 527
Gender Effects in Pharmacokinetics and Pharmacodynamics
Harris, R. Z., Benet, L. Z., & Schwartz, J. B. (1995) · Drugs · doi:10.2165/00003495-199550020-00003 · Cited by 504
Effects of the Antifungal Agents on Oxidative Drug Metabolism: Clinical Relevance
Venkatakrishnan, K., von Moltke, L. L., & Greenblatt, D. J. (2000) · Clinical Pharmacokinetics · doi:10.2165/00003088-200038020-00002 · Cited by 508
Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs
Wang, D., Guo, Y., Wrighton, S. A., Cooke, G., & Sadée, W. (2010) · The Pharmacogenomics Journal · doi:10.1038/tpj.2010.28 · Cited by 507
Enzyme-Catalyzed Activation of Anticancer Prodrugs
Rooseboom, M., Commandeur, J. N. M., & Vermeulen, N. P. E. (2004) · Pharmacological Reviews · doi:10.1124/pr.56.1.3 · Cited by 503
“, from 5 4 pmol/mg for 2D6 to 96 51 pmol/mg for 3A determined from 60 individuals (Shimada et al., 1994).”
BackgroundHsu, A., Granneman, G. R., & Bertz, R. (1998) · Clinical Pharmacokinetics · doi:10.2165/00003088-199835040-00002 · Cited by 486
Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data
Iwatsubo, T., Hirota, N., Ooie, T., Suzuki, H., Shimada, N., Chiba, K., Ishizaki, T., Green, C. E., Tyson, C. A., & Sugiyama, Y. (1997) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(96)00184-2 · Cited by 479
The importance of drug interactions in epilepsy therapy
Patsalos, P. N., Fröscher, W., Pisani, F., & Van Rijn, C. M. (2002) · Epilepsia · doi:10.1046/j.1528-1157.2002.13001.x · Cited by 455
Lee, A. J., Cai, M. X., Thomas, P. E., Conney, A. H., & Zhu, B. T. (2003) · Endocrinology · doi:10.1210/en.2003-0192 · Cited by 457
How Important Are Gender Differences in Pharmacokinetics?
Meibohm, B., Beierle, I., & Derendorf, H. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241050-00002 · Cited by 454
“ity were lacking in in vitro studies with human liver microsomes.[78,79] Similarly, no gender effects”
BackgroundPharmacokinetic/Pharmacodynamic Profile of Posaconazole
Li, Y., Theuretzbacher, U., Clancy, C. J., Nguyen, M. H., & Derendorf, H. (2010) · Clinical Pharmacokinetics · doi:10.2165/11319340-000000000-00000 · Cited by 452
Clinical Pharmacokinetics of Cyclophosphamide
de Jonge, M. E., Huitema, A. D. R., Rodenhuis, S., & Beijnen, J. H. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544110-00003 · Cited by 447
Schiffer, L., Barnard, L., Baranowski, E. S., Gilligan, L. C., Taylor, A. E., Arlt, W., Shackleton, C. H. L., & Storbeck, K.-H. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105439 · Cited by 450
“CYP3A4 is the most abundant CYP expressed in the adult liver [121,122] and makes the major contribution to steroid metabolism.”
Biotransformation of Xenobiotics
Timbrell, J. A., & Marrs, T. C. (2009) · General, Applied and Systems Toxicology · doi:10.1002/9780470744307.gat004 · Cited by 435
Ohtsuki, S., Schaefer, O., Kawakami, H., Inoue, T., Liehner, S., Saito, A., Ishiguro, N., Kishimoto, W., Ludwig-Schwellinger, E., Ebner, T., et al. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.042259 · Cited by 440
“…processes have been a focus of interest for pharmacokinetic research for a long time and have been analyzed in attempts to evaluate individual differences of hepatic disposition and metabolism (Shimada et al., 1994; Parkinson et al., 2004; Meier et al., 2006; Johansson and Ingelman-Sundberg, 2011).”
BackgroundIshizaki, & Horai (1999) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.1999.00022.x · Cited by 429
Wacher, V. J., Silverman, J. A., Zhang, Y., & Benet, L. Z. (1998) · Journal of Pharmaceutical Sciences · doi:10.1021/js980082d · Cited by 423
Gorski, J. C., Jones, D. R., HAEHNERDANIELS, B., Hamman, M. A., O'Mara, E. M., & Hall, S. D. (1998) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(98)90146-1 · Cited by 409
The ontogeny of drug metabolism enzymes and implications for adverse drug events
Hines, R. N. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.02.005 · Cited by 408
Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice
Gardiner, S. J., & Begg, E. J. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.6 · Cited by 406
“This enzyme has undergone comparatively little study, possibly because it was thought to be absent in some livers and present in low (perhaps unimportant) levels in others (Mimura et al., 1993; Shimada et al., 1994).”
BackgroundHesse, L. M., Venkatakrishnan, K., Court, M. H., Moltke, L. L., Duan, S., Shader, R. I., & Greenblatt, D. J. (2000) · Drug Metabolism and Disposition · doi:10.1016/s0026-895x(24)12046-9 · Cited by 398
“Earlier immunoquantification studies suggested that CYP2B6 comprised less than 1% of total hepatic P450, and CYP2B6 was concluded to be a minor CYP isoform (Shimada et al., 1994).”
Interactions of Herbs with Cytochrome P450
Zhou, S.-F., Gao, Y.-H., Jiang, W.-Q., Huang, M., Xu, A., & Paxton, J. (2003) · Drug metabolism reviews (Softcover ed.) · doi:10.1081/dmr-120018248 · Cited by 404
“(Rendic and Di Carlo, 1997; Shimada et al., 1994).”
Aitken, A. E., & Morgan, E. T. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.015511 · Cited by 407
The utility of the minipig as an animal model in regulatory toxicology
Bode, G., Clausing, P., Gervais, F., Løgsted, J., Luft, J., Nogués, V., & Sims, J. (2010) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2010.05.009 · Cited by 399
Age-Related Pharmacokinetic and Pharmacodynamic Changes and Related Risk of Adverse Drug Reactions
Corsonello, A., Pedone, C., & Incalzi, R. A. (2010) · Current Medicinal Chemistry · doi:10.2174/092986710790416326 · Cited by 402
“Such a finding has not been confirmed for the CYP3A subfamily, which is responsible for the elimination of more than 50% of its substrates [72-74].”
BackgroundKot, M., & Daniel, W. A. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.05.025 · Cited by 389
Parkinson, A. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2004.01.010 · Cited by 385
Identification of the Cytochrome P450 Enzymes Involved in the N-Oxidation of Voriconazole
Hyland, R., Jones, B. C., & Smith, D. A. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.5.540 · Cited by 386
“Of these enzymes, the greatest effect is likely to be observed with modulators of CYP3A4, which is also the major P450 enzyme present in human liver (Shimada et al., 1994).”
Cytochromes P450, Drugs, and Diseases
Guengerich, F. P. (2003) · Molecular Interventions · doi:10.1124/mi.3.4.194 · Cited by 379
Self-citationDrug Metabolites in Safety Testing
Baillie, T. A. (2002) · Toxicology and Applied Pharmacology · doi:10.1006/taap.2002.9440 · Cited by 371
Preskorn, S. H. (1997) · Clinical Pharmacokinetics · doi:10.2165/00003088-199700321-00003 · Cited by 370
Bogaards, J. J. P., Bertrand, M., Jackson, P., Oudshoorn, M., Weaver, R. J., van BLADEREN, P. J., & Walther, B. (2000) · Xenobiotica · doi:10.1080/00498250010021684 · Cited by 369
The Ontogeny of Human Drug-Metabolizing Enzymes: Phase I Oxidative Enzymes
Hines, R. N., & McCarver, D. G. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.300.2.355 · Cited by 364
“Of these, the enzymes encoded by CYP2C9 and CYP2C19 are the most abundant in adult human liver (Shimada et al., 1994).”
BackgroundInfluentialResearch progress on berberine with a special focus on its oral bioavailability
Liu, C.-S., Zheng, Y.-R., Zhang, Y.-F., & Long, X.-Y. (2016) · Fitoterapia · doi:10.1016/j.fitote.2016.02.001 · Cited by 363
Clinically Significant Pharmacokinetic Interactions Between Dietary Caffeine and Medications
Carrillo, J. A., & Benítez, J. (2000) · Clinical Pharmacokinetics · doi:10.2165/00003088-200039020-00004 · Cited by 370
“[50-53] The regulatory mechanisms of CYP1A1 induction involve transcriptional events and have been thoroughly elucidated.”
BackgroundRiches, Z., Stanley, E. L., Bloomer, J. C., & Coughtrie, M. W. H. (2009) · Drug Metabolism and Disposition · doi:10.1124/dmd.109.028399 · Cited by 365
“Immunochemical quantification of expression profiles has been carried out for the cytochromes P450 (P450s) in liver (Shimada et al., 1994) and intestine (Paine et al.”
BackgroundMethodInhibition and induction of human cytochrome P450 (CYP) enzymes
Pelkonen, O., MÄEENPÄEÄ, J., Taavitsainen, P., Rautio, A., & Raunio, H. (1998) · Xenobiotica · doi:10.1080/004982598238886 · Cited by 358
Caraco, Y., Blotnick, S., & Muszkat, M. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100316 · Cited by 359
Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms
Ingelman‐Sundberg, M. (2004) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-003-0819-z · Cited by 355
Faucette, S. R., Hawke, R. L., LeCluyse, E. L., Shord, S. S., Yan, B., Laethem, R. M., & Lindley, C. M. (2000) · Drug Metabolism and Disposition · doi:10.1016/s0026-895x(24)12054-8 · Cited by 354
“differences (Shimada et al., 1994; Kim et al., 1997) in CYP2B6 expression have been recognized.”
Is the Role of the Small Intestine in First-Pass Metabolism Overemphasized?
Lin, J. H., Chiba, M., & Baillie, T. A. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01402-9 · Cited by 351
“The average total cytochrome P-450 content in human intestine, about 20 pmol/mg microsomal protein, was found to be much lower than that in the liver (300 pmol/mg microsomal protein) (Peters and Kremers, 1989; Shimada et al., 1994).”
Activation and detoxication of aflatoxin B1
Guengerich, F. P., Johnson, W. W., Shimada, T., et al. (1998) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(97)00289-3 · Cited by 345
Self-citationBièche, I., Narjoz, C., Asselah, T., Vacher, S., Marcellin, P., Lidereau, R., Beaune, P. H., & de Waziers, I. (2007) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32810f2e58 · Cited by 339
CYP2C9 allelic variants: ethnic distribution and functional significance
Xie, H., Prasad, H. C., Kim, R. B., et al. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00076-5 · Cited by 339
Eagling, V. A., Tjia, J. F., & Back, D. J. (1998) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.1998.00679.x · Cited by 337
Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species
Guengerich, F. P. (1997) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(97)00068-9 · Cited by 329
Self-citationOntogeny of Hepatic and Renal Systemic Clearance Pathways in Infants
Alcorn, J., & McNamara, P. J. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241120-00003 · Cited by 336
Varma, M. V. S., Obach, R. S., Rotter, C. J., Miller, H., Chang, G., Steyn, S. J., El‐Kattan, A. F., & Troutman, M. D. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm901371v · Cited by 349
Yuan, R., Madani, S., Wei, X., et al. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.12.1311 · Cited by 327
“(Shimada et al., 1994), it is responsible for metabolizing drugs in a”
BackgroundInfluentialDevelopmental Expression of Human Hepatic CYP2C9 and CYP2C19
Koukouritaki, S. B., Manro, J. R., Marsh, S. A., Stevens, J. C., Rettie, A. E., McCarver, D. G., & Hines, R. N. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.060137 · Cited by 327
“…content in the oldest age bracket (>5 mos through 18 yrs; N = 79; median = 5.0 yrs) of 18.0 ± 6.0 pmol/mg microsomal protein is significantly less than the total CYP2C specific content of 60 ± 27 pmol/mg protein (N=60; median age=54.5 yrs) reported by Shimada et al. (1994) (ANOVA, p < 0.001).”
BackgroundMethodInfluentialTranscriptional Control of Intestinal Cytochrome P-4503A by 1α,25-Dihydroxy Vitamin D3
Thummel, K. E., Brimer, C., Yasuda, K., Thottassery, J. V., Senn, T., Lin, Y., Ishizuka, H., Kharasch, E. D., Schuetz, J. D., & Schuetz, E. G. (2001) · Molecular Pharmacology · doi:10.1124/mol.60.6.1399 · Cited by 325
Mechanisms of Clinically Relevant Drug Interactions Associated with Tacrolimus
Christians, U., Jacobsen, W., Benet, L. Z., & Lampen, A. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241110-00003 · Cited by 324
Anderson, G. D. (2005) · Journal of Women s Health · doi:10.1089/jwh.2005.14.19 · Cited by 320
Roy, P., Yu, L. J., Crespi, C. L., & Waxman, D. J. (1999) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(24)15302-0 · Cited by 321
“However, the catalytic contribution of 3A5 and 3A7 to adult human liver oxazaphosphorine activation is likely minor compared with 3A4, in view of the absence or low level of 3A5 in a majority of human livers (Shimada et al., 1994) and the preferential expression of 3A7 in fetal liver tissue (Schuetz et al.”
BackgroundResultInfluentialEnzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction
Thummel, K. E. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(97)00039-2 · Cited by 318
Induction of CYP2C genes in human hepatocytes in primary culture.
Gerbal‐Chaloin, S., Pascussi, J., Pichard‐Garcia, L., Daujat‐Chavanieu, M., Waechter, F., Fabre, J.-M., Carrère, N., & Maurel, P. (2001) · PubMed · Cited by 318
Common allelic variants of cytochrome P4503A4 and their prevalence in different populations
Lamba, J. K., Lin, Y. S., Thummel, K. E., et al. (2002) · Pharmacogenetics · doi:10.1097/00008571-200203000-00006 · Cited by 316
Pharmacogenetics of Warfarin Elimination and Its Clinical Implications
Takahashi, H., & Echizen, H. (2001) · Clinical Pharmacokinetics · doi:10.2165/00003088-200140080-00003 · Cited by 312
Yamazaki, H., & Shimada, T. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.0302 · Cited by 310
Self-citationHuman Drug Metabolism and the Cytochromes P450: Application and Relevance of In Vitro Models
Venkatakrishnan, K., Moltke, L. L., & Greenblatt, D. J. (2001) · The Journal of Clinical Pharmacology · doi:10.1177/00912700122012724 · Cited by 309
“CYP2A6 may participate in procarcinogen activation but has a relatively minor role in drug biotransformation and accounts for only approximately 4% of total immunoquantified human hepatic CYP.7 CYP2A6 is a coumarin 7-hydroxylase, partici- pates in nicotine metabolism, and contributes to the reductive metabolism of the…”
BackgroundInfluentialChauret, N., Gauthier, A., & Nicoll‐Griffith, D. A. (1998) · PubMed · Cited by 309
Metadata
- Authors
- Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., & Guengerich, F. P.
- Affiliations
- Osaka Prefectural Institute of Public Health (JP)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1994-07
- Volume
- 270
- Issue
- 1
- Pages
- 414-423
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2155268095
- Cited by
- 2,785
- References
- 0
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 24 · 2023: 40 · 2022: 36 · 2021: 55 · 2020: 41 · 2019: 59 · 2018: 52 · 2017: 53 · 2016: 75 · 2015: 81 · 2014: 121 · 2013: 104 · 2012: 118
- FWCI
- 64.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institutes of Health (5r35ca044353-14)
- National Cancer Institute (CA 44353)
- National Institute of Environmental Health Sciences (ES00267)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Keywords
- cytochrome P450, interindividual variability, liver microsomes, CYP1A2, CYP2A6, CYP2B6, CYP2C, CYP2D6, CYP2E1, CYP3A4, monooxygenase activity, procarcinogen metabolism, drug metabolism, sex differences
- MeSH terms
- Adolescent, Adult, Aged, Aging, Biotransformation, Carcinogens, Child, Cytochrome P-450 Enzyme System, Pharmaceutical Preparations, Female, Humans, Individuality, Infant, Isoenzymes, Japan, Liver, Male, Microsomes, Liver, Middle Aged, Oxidation-Reduction, Sex Factors, Hazardous Substances, White People
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
