Редактирование: CYP2A6 (раздел)

==Publications==

{{medline-entry
|title=Analysis of the variability of the pharmacokinetics of multiple drugs in young adult and elderly subjects and its implications for acceptable daily exposures and cleaning validation limits.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28396010
|abstract=The elderly constitute a significant, potentially sensitive, subpopulation within the general population, which must be taken into account when performing risk assessments including determining an acceptable daily exposure (ADE) for the purpose of a cleaning validation. Known differences in the pharmacokinetics of drugs between young adults (who are typically the subjects recruited into clinical trials) and the elderly are potential contributors affecting the interindividual uncertainty factor (UF ) component of the ADE calculation. The UF  values were calculated for 206 drugs for young adult and elderly groups separately and combined (with the elderly assumed to be a sensitive subpopulation) from published studies where the pharmacokinetics of the young adult and elderly groups were directly compared. Based on the analysis presented here, it is recommended to use a default UF  value of 10 for worker populations (which are assumed to be approximately equivalent to the young adult groups) where no supporting pharmacokinetic data exist, while it is recommended to use a default UF  value of 15 for the general population, to take the elderly into consideration when calculating ADE values. The underlying reasons for the large differences between the exposures in the young adult and elderly subjects for the 10 compounds which show the greatest separation are different in almost every case, involving the OCT2 transporter, glucuronidation, hydrolysis, [[CYP1A2]], [[CYP2A6]], [[CYP2C19]], [[CYP2D6]], [[CYP3A4]] or [[CYP3A5]]. Therefore, there is no consistent underlying mechanism which appears responsible for the largest differences in pharmacokinetic parameters between young adult and elderly subjects.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Cytochrome P-450 Enzyme System
* Female
* Humans
* Male
* Middle Aged
* Organic Cation Transporter 2
* Pharmacokinetics
* Risk Assessment
* Uncertainty
* Young Adult
|keywords=* Acceptable daily exposure
* Cleaning validation
* Elderly
* Pharmacokinetics
|full-text-url=https://sci-hub.do/10.1016/j.ijheh.2017.03.007
}}
{{medline-entry
|title=Sex- and age-dependent gene expression in human liver: An implication for drug-metabolizing enzymes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28153492
|abstract=Sex and age differences in hepatic expression of drug-metabolizing enzyme genes could cause variations in drug metabolism, but has not been fully elucidated, especially in Asian population. In this study, the global expression of human hepatic genes was analyzed by microarrays in 40 Japanese subjects (27 males and 13 females). Thirty-five sex-biased genes were identified (P < 0.005). Whereas, 60 age-biased genes in two age groups, <60 years and ≥70 years (P < 0.001), were identified in males. By Gene Ontology analysis, the sex-biased genes were related to protein catabolism and modification, while the age-biased genes were related to transcription regulation and cell death. Quantitative polymerase chain reaction confirmed the female-biased expression of drug-metabolizing enzyme genes BChE, [[CYP4X1]], and [[SULT1E1]] (≥1.5-fold, P < 0.05). Further analysis of drug-metabolizing enzyme genes indicated that expression of [[CYP2A6]] and [[CYP3A4]] in females in the ≥70 age group was less than in the <60 age group (≥1.5-fold, P < 0.05), and this trend was also observed for PXR expression in males (≥1.5-fold, P < 0.05). The results presented provide important insights into hepatic physiology and function, especially drug metabolism, with respect to sex and age.
|mesh-terms=* Aged
* Aging
* Butyrylcholinesterase
* Cytochrome P-450 Enzyme System
* Female
* Gene Expression Profiling
* Gene Expression Regulation, Enzymologic
* Humans
* Liver
* Male
* Middle Aged
* Oligonucleotide Array Sequence Analysis
* Pharmaceutical Preparations
* Pregnane X Receptor
* Receptors, Steroid
* Sex Characteristics
* Sulfotransferases
|keywords=* Age
* Cytochrome P450
* Drug metabolism
* Gene expression
* Liver
* Sex
|full-text-url=https://sci-hub.do/10.1016/j.dmpk.2016.10.409
}}