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Correlation of Body...
Correlation of Body Weight and Composition With Hepatic Activities of Cytochrome P450 Enzymes
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Krogstad, V. (author)
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Peric, A. (author)
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Robertsen, I. (author)
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Kringen, M. K. (author)
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Vistnes, M. (author)
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Hjelmesaeth, J. (author)
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Sandbu, R. (author)
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Johnson, L. K. (author)
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Angeles, P. C. (author)
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Jansson-Lofmark, R. (author)
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- Karlsson, Cecilia, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Andersson, S. (author)
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Asberg, A. (author)
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Andersson, T. B. (author)
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Christensen, H. (author)
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 110:1, s. 432-437
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http://jpharmsci.org...
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Abstract
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- Obesity is associated with comorbidities of which pharmacological treatment is needed. Physiological changes associated with obesity may influence the pharmacokinetics of drugs, but the effect of body weight on drug metabolism capacity remains uncertain. The aim of this study was to investigate ex vivo activities of hepatic drug metabolizing CYP enzymes in patients covering a wide range of body weight. Liver biopsies from 36 individuals with a body mass index (BMI) ranging from 18 to 63 kg/m(2) were obtained. Individual hepatic microsomes were prepared and activities of CYP3A, CYP2B6, CYP2C8, CYP2D6, CYP2C9, CYP2C19 and CYP1A2 were determined. The unbound intrinsic clearance (C-Lint,C-u) values for CYP3A correlated negatively with body weight (r = -0.43, p < 0.01), waist circumference (r = -0.47, p < 0.01), hip circumference (r = -0.51, p < 0.01), fat percent (r = -0.41, p < 0.05), fat mass (r = -0.48, p < 0.01) and BMI (r = -0.46, p < 0.01). Linear regression analysis showed that C-Lint,C-u values for CYP3A decreased with 5% with each 10% increase in body weight (r(2) = 0.12, beta = -0.558, p < 0.05). There were no correlations between body weight measures and CLint,u values for the other CYP enzymes investigated. These results indicate reduced hepatic metabolizing capacity of CYP3A substrates in patients with increasing body weight. (C) 2020 The Authors. Published by Elsevier Inc.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- Cytochrome P450 (CYP)
- Drug metabolizing enzyme(s)
- First-pass
- metabolism
- Hepatic metabolism
- Human liver microsomes
- Phase I
- metabolism
- consortium cpic guidelines
- morbidly obese-patients
- cyp3a4 expression
- pharmacokinetics
- midazolam
- liver
- epidemiology
- disposition
- cytokines
- impact
- Pharmacology & Pharmacy
- Chemistry
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Krogstad, V.
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Peric, A.
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Robertsen, I.
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Kringen, M. K.
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Vistnes, M.
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Hjelmesaeth, J.
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show more...
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Sandbu, R.
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Johnson, L. K.
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Angeles, P. C.
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Jansson-Lofmark, ...
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Karlsson, Cecili ...
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Andersson, S.
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Asberg, A.
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Andersson, T. B.
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Christensen, H.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmacology and ...
- Articles in the publication
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Journal of Pharm ...
- By the university
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University of Gothenburg
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Karolinska Institutet