Cited by 2,785Pharmacogenetics and Drug MetabolismDrug-Induced Hepatotoxicity and ProtectionMetal-Catalyzed Oxygenation Mechanisms

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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

Shimada, T, Yamazaki, H, Mimura, M, Inui, Y, Guengerich, F P·1994·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1016/s0022-3565(25)22379-5

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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.

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Active secretion and enterocytic drug metabolism barriers to drug absorption1PII of original article: S0169-409X(96)003304. The article was originally published in Advanced Drug Delivery Reviews 20 (1996) 99–112.1
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Kimura, Y., Ito, H., Ohnishi, R., & Hatano, T. (2009) · Food and Chemical Toxicology · doi:10.1016/j.fct.2009.10.041 · Cited by 234
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Desta, Z., El‐Boraie, A., Gong, L., Somogyi, A. A., Lauschke, V. M., Dandara, C., Klein, K., Miller, N., Klein, T. E., Tyndale, R. F., et al. (2021) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2166 · Cited by 237
“Until the end of 1990s, CYP2B6 was thought to be an insignificant component of the hepatic P450 system, as earlier studies reported very low or undetectable CYP2B6 protein expression in a significant proportion of human liver tissues, in part due to a lack of reliable antibodies.(7) However, after specific antibodies…”
Roles of NADPH-P450 Reductase and Apo- and Holo-Cytochrome b5 on Xenobiotic Oxidations Catalyzed by 12 Recombinant Human Cytochrome P450s Expressed in Membranes of Escherichia coli
Yamazaki, H., Nakamura, M., Komatsu, T., Ohyama, K., Hatanaka, N., Asahi, S., Shimada, N., Guengerich, F. P., Shimada, T., Nakajima, M., et al. (2002) · Protein Expression and Purification · doi:10.1006/prep.2001.1578 · Cited by 234
Self-citation
Population distribution and effects on drug metabolism of a genetic variant in the 5′ promotor region of CYP3A4
Ball, S. E., Scatina, J., Kao, J., et al. (1999) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(99)70037-8 · Cited by 233
Xenobiotic-metabolizing cytochrome P450 enzymes in the human feto-placental unit: role in intrauterine toxicity
Hakkola, J., Pelkonen, O., Pasanen, M., & Raunio, H. (1998) · Critical Reviews in Toxicology · doi:10.1080/10408449891344173 · Cited by 229
Gender differences in drug effects: implications for anesthesiologists
Pleym, H., Spigset, O., Kharasch, E. D., & Dale, O. (2003) · Acta Anaesthesiologica Scandinavica · doi:10.1034/j.1399-6576.2003.00036.x · Cited by 230
Present and future in vitro approaches for drug metabolism
Ekins, S., Ring, B. J., Grace, J. E., Belle, D. J., & Wrighton, S. A. (2000) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/s1056-8719(00)00110-6 · Cited by 228
Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene
Gellner, K., Eiselt, R., Hustert, E., Arnold, H., Koch, I., Haberl, M., Deglmann, C. J., Burk, O., Buntefuss, D., Escher, S., et al. (2001) · Pharmacogenetics · doi:10.1097/00008571-200103000-00002 · Cited by 226
Metabolic activation of polycyclic aromatic hydrocarbons and other procarcinogens by cytochromes P450 1A1 and P450 1B1 allelic variants and other human cytochromes P450 in Salmonella typhimurium NM2009.
Shimada, T., Oda, Y., Gillam, E. M. J., et al. (2001) · PubMed · Cited by 226
Self-citation
Cytochrome P450 2C8: Substrates, inhibitors, pharmacogenetics, and clinical relevance
Totah, R. A., & Rettie, A. E. (2005) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2004.12.267 · Cited by 225
Structures of Human Cytochrome P-450 2E1
Porubsky, P. R., Meneely, K. M., & Scott, E. E. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805999200 · Cited by 232
Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: Role of phenolic hydroxyl groups in the resorcinol moiety
Yamaori, S., Ebisawa, J., Okushima, Y., Yamamoto, I., & Watanabe, K. (2011) · Life Sciences · doi:10.1016/j.lfs.2011.02.017 · Cited by 222
“human livers (Shimada et al., 1994), is capable of metabolizing structurally diverse compounds, such as diltiazem, midazolam, erythromycin, and cyclosporine (Rendic, 2002).”
Background
Evaluation of the selectivity of In vitro probes and suitability of organic solvents for the measurement of human cytochrome P450 monooxygenase activities.
Hickman, D., Wang, J. P., Wang, Y., & Unadkat, J. D. (1998) · PubMed · Cited by 222
Psychotropic Drugs, Cardiac Arrhythmia, and Sudden Death
Witchel, H. J., Hancox, J. C., & Nutt, D. (2003) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200302000-00010 · Cited by 219
Predicting drug clearance from recombinantly expressed CYPs: intersystem extrapolation factors
Proctor, N. J., Tucker, G. T., & Rostami-Hodjegan, A. (2004) · Xenobiotica · doi:10.1080/00498250310001646353 · Cited by 219
“Typically, the average abundance of each CYP has been used (e.g. from Shimada et al. 1994).”
Method
Pharmacokinetic-Pharmacodynamic Crisis in the Elderly
ELDesoky, E. S. (2006) · American Journal of Therapeutics · doi:10.1097/01.mjt.0000183719.84390.4d · Cited by 220
“In vitro studies of hepatic microsomes showed no significant differences in CYP activity and/or inducibility as a function of age.(32,33) On the other hand, in vivo studies showed equivocal results (a decrease or no change) in hepatic drug clearance by different CYP isoforms in the elderly, as shown in Table 2.”
Result
Differences in Drug Pharmacokinetics Between East Asians and Caucasians and the Role of Genetic Polymorphisms
Kim, K., Johnson, J. A., & Derendorf, H. (2004) · The Journal of Clinical Pharmacology · doi:10.1177/0091270004268128 · Cited by 220
“CYP3A4 is the most predominant form and is expressed at about 30% of the total CYP abundance in the liver, and it is also the major CYP expressed in the GI tract.(308) Although it is expressed in other tissues such as the kidney, the liver and gut are major sites regarding drugs and other xenobiotic chemicals.”
Background
Human Cytochrome P450 Enzymes
Guengerich, F. P. (2007) · Springer eBooks · doi:10.1007/0-387-27447-2_10 · Cited by 226
Self-citation
Intracrine androgen biosynthesis, metabolism and action revisited
Schiffer, L., Arlt, W., & Storbeck, K.-H. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.08.016 · Cited by 217
“CYP3A4 is the most abundant P450 in the liver (~30%) (Shimada et al., 1994) and”
Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4.
Hustert, E., Zibat, A., Presecan, E., Eiselt, R., Mueller, R., Fuss, C., Brehm, I., Brinkmann, U., Eichelbaum, M. F., Wojnowski, L., et al. (2001) · PubMed · Cited by 218
Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation
Xie, H.-J., Yaşar, Ü., Lundgren, S., Griškevičius, L., Terelius, Y., Hassan, M., & Rane, A. (2003) · The Pharmacogenomics Journal · doi:10.1038/sj.tpj.6500157 · Cited by 215
Photocatalytic performance of g-C3N4 based nanocomposites for effective degradation/removal of dyes from water and wastewater
Ahmaruzzaman, M., & Mishra, S. R. (2021) · Materials Research Bulletin · doi:10.1016/j.materresbull.2021.111417 · Cited by 214
Comprehensive characterization of cytochrome P450 isozyme selectivity across chemical libraries
Veith, H., Southall, N. T., Huang, R., James, T., Fayne, D., Artemenko, N. V., Shen, M., Inglese, J., Austin, C. P., Lloyd, D. G., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1581 · Cited by 222
Board-invited review: St. Anthony's Fire in livestock: causes, mechanisms, and potential solutions.
Strickland, J., Looper, M., Matthews, J. C., Rosenkrans, C., Flythe, M., & Brown, K. (2011) · Journal of Animal Science · doi:10.2527/jas.2010-3478 · Cited by 205
“, drug, toxicant) metabolism, CYP3A4 is very active in xenobiotic metabolism and is the predominant P450 in human liver and intestine, reportedly comprising up to 60% of total CYP450 (Shimada et al., 1994; McKinnon et al., 1995).”
Background

Authors: Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., & Guengerich, F. P.
Affiliations: Osaka Prefectural Institute of Public Health (JP)
ORCID: Shimada, T
Yamazaki, H
Guengerich, F P
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)
DOI: 10.1016/s0022-3565(25)22379-5
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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

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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

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