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Variance of microsomal protein and cytochrome P450 2E1 and 3A forms in adult human liver.

Authors
Lipscomb-JC; Teuschler-LK; Swartout-JC; Striley-CAF; Snawder-JE
Source
Toxicol Mech Methods 2003 Jan; 13(1):45-51
NIOSHTIC No.
20033230
Abstract
Differences in the pharmacokinetics of xenobiotics among humans makes them differentially susceptible to risk. Differences in enzyme content can mediate pharmacokinetic differences. Microsomal protein is often isolated from liver to characterize enzyme content and activity, but no measures exist to extrapolate these data to the intact liver. Measures were developed from up to 60 samples of adult human liver to characterize the content of microsomal protein and cytochrome P450 (CYP) enzymes. Statistical evaluations are necessary to estimate values far from the mean value. Adult human liver contains 52.9 +/-1.476 mg microsomal protein per g; 2587 +/-1.84 pmoles CYP2E1 per g; and 5237 +/-2.214 pmols CYP3A per g (geometric mean +/-geometric standard deviation). These values are useful for identifying and testing susceptibility as a function of enzyme content when used to extrapolate in vitro rates of chemical metabolism for input to physiologically based pharmacokinetic models which can then be exercised to quantify the effect of variance in enzyme expression on risk-relevant pharmacokinetic outcomes.
Keywords
Liver-cells; Liver-function; Liver-microsomal-enzymes; Liver-microsomal-metabolism; Liver-microsomes; Humans; Physiological-chemistry; Physiological-effects; Physiological-factors; Physiological-function; Physiological-response; Physiological-testing; Pharmacodynamics
CODEN
TMMOCP
Publication Date
20030101
Document Type
Journal Article
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1537-6524
NIOSH Division
DART
Source Name
Toxicology Mechanisms and Methods
State
OH
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