Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver
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作者:
Wilson, ZE
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Univ Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, EnglandUniv Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, England
Wilson, ZE
[1
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Rostami-Hodjegan, A
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Univ Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, EnglandUniv Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, England
Rostami-Hodjegan, A
[1
]
Burn, JL
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Univ Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, EnglandUniv Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, England
Burn, JL
[1
]
Tooley, A
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Univ Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, EnglandUniv Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, England
Tooley, A
[1
]
Boyle, J
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Univ Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, EnglandUniv Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, England
Boyle, J
[1
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Ellis, SW
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Univ Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, EnglandUniv Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, England
Ellis, SW
[1
]
Tucker, GT
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Univ Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, EnglandUniv Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, England
Tucker, GT
[1
]
机构:
[1] Univ Sheffield, Div Clin Sci S, Liver Grp, Sheffield, S Yorkshire, England
liver microsomes;
prediction of metabolic clearance;
cytochrome P450;
in silico ADME;
variability in metabolism;
D O I:
10.1046/j.1365-2125.2003.01881.x
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
Aims To determine levels of microsomal protein (MPPGL) and hepatocellularity (HPGL) per gram of human liver and their interindividual variability. Methods Triplicate liver samples were used to determine values of MPPGL (n = 20) and HPGL ( n = 7) after accounting for the fractional loss of microsomal protein or hepatocytes during processing. Repeated measurements from each liver sample allowed the estimation of true interindividual variability in MPPGL and HPGL using ANOVA. Results The value of MPPGL ranged from 26 to 54 mg g(-1) (mean(geo) = 33 mg g(-1)). The value of HPGL ranged from 65 to 185 x 10(6) cells g(-1) (mean(geo) = 107 x 10(6) cells g(-1)). Conclusions There is significant interindividual variability in MPPGL, which has implications for the accurate extrapolation of in vitro data on drug metabolism to predict in vivo metabolic clearance.
机构:
Univ Sheffield, Unit Mol Pharmacol & Pharmacogenet, Sheffield, S Yorkshire, EnglandUniv Sheffield, Unit Mol Pharmacol & Pharmacogenet, Sheffield, S Yorkshire, England
Wilson, ZE
Tooley, A
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Univ Sheffield, Unit Mol Pharmacol & Pharmacogenet, Sheffield, S Yorkshire, EnglandUniv Sheffield, Unit Mol Pharmacol & Pharmacogenet, Sheffield, S Yorkshire, England
Tooley, A
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机构:
Rostami-Hodjegan, A
Ellis, SW
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机构:
Univ Sheffield, Unit Mol Pharmacol & Pharmacogenet, Sheffield, S Yorkshire, EnglandUniv Sheffield, Unit Mol Pharmacol & Pharmacogenet, Sheffield, S Yorkshire, England
Ellis, SW
Tucker, GT
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机构:
Univ Sheffield, Unit Mol Pharmacol & Pharmacogenet, Sheffield, S Yorkshire, EnglandUniv Sheffield, Unit Mol Pharmacol & Pharmacogenet, Sheffield, S Yorkshire, England
机构:
Ege Univ, Fac Med, Dept Urol, TR-35100 Izmir, TurkeyEge Univ, Fac Pharm, Dept Toxicol, TR-35100 Izmir, Turkey
Turna, Burak
Sozbilen, Murat
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机构:
Ege Univ, Fac Med, Dept Gen Surg, TR-35100 Izmir, Turkey
Med Pk Hosp, Dept Gen Surg, Karsiyaka Izmir, TurkeyEge Univ, Fac Pharm, Dept Toxicol, TR-35100 Izmir, Turkey
Sozbilen, Murat
Orhan, Hilmi
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Ege Univ, Fac Pharm, Dept Toxicol, TR-35100 Izmir, TurkeyEge Univ, Fac Pharm, Dept Toxicol, TR-35100 Izmir, Turkey
机构:
Univ Sheffield, Royal Hallamshire Hosp, Unit Mol Pharmacol & Pharmacogenet, Sheffield S10 2JF, S Yorkshire, EnglandUniv Sheffield, Royal Hallamshire Hosp, Unit Mol Pharmacol & Pharmacogenet, Sheffield S10 2JF, S Yorkshire, England
Wilson, ZE
Tooley, A
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机构:
Univ Sheffield, Royal Hallamshire Hosp, Unit Mol Pharmacol & Pharmacogenet, Sheffield S10 2JF, S Yorkshire, EnglandUniv Sheffield, Royal Hallamshire Hosp, Unit Mol Pharmacol & Pharmacogenet, Sheffield S10 2JF, S Yorkshire, England
Tooley, A
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Rostami-Hodjegan, A
Ellis, SW
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机构:
Univ Sheffield, Royal Hallamshire Hosp, Unit Mol Pharmacol & Pharmacogenet, Sheffield S10 2JF, S Yorkshire, EnglandUniv Sheffield, Royal Hallamshire Hosp, Unit Mol Pharmacol & Pharmacogenet, Sheffield S10 2JF, S Yorkshire, England
Ellis, SW
Tucker, GT
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sheffield, Royal Hallamshire Hosp, Unit Mol Pharmacol & Pharmacogenet, Sheffield S10 2JF, S Yorkshire, EnglandUniv Sheffield, Royal Hallamshire Hosp, Unit Mol Pharmacol & Pharmacogenet, Sheffield S10 2JF, S Yorkshire, England