Редактирование: CYP3A7 (раздел)

==Publications==

{{medline-entry
|title=Dynamics of Cytosine Methylation in the Proximal Promoters of [[CYP3A4]] and [[CYP3A7]] in Pediatric and Prenatal Livers.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26772622
|abstract=Members of the human CYP3A family of metabolizing enzymes exhibit developmental changes in expression whereby [[CYP3A7]] is expressed in fetal tissues, followed by a transition to expression of [[CYP3A4]] in the first months of life. Despite knowledge about the general pattern of CYP3A activity in human development, the mechanisms that regulate developmental expression remain poorly understood. Epigenetic changes, including cytosine methylation, have been suggested to play a role in the regulation of CYP3A expression. The objective of this study was to investigate changes in cytosine methylation of the [[CYP3A4]] and [[CYP3A7]] genes in human pediatric and prenatal livers. The methylation status of cytosine-phospho-guanine dinucleotides was determined in 16 pediatric liver samples using methyl-seq and confirmed by bisulfite sequencing of 48 pediatric and 34 prenatal liver samples. Samples were separated by age into five groups (prenatal, < 1 year of age, 1.8-6 years, 7-11 years, and 12-17 years). Methyl-seq anaylsis revealed that cytosines in the proximal promoter of [[CYP3A7]] are hypomethylated in neonates compared with adolescents (P < 0.001). In contrast, a cytosine 383 base pair upstream of [[CYP3A4]] is hypermethylated in liver samples from neonates compared with adolescents (P = 0.00001). Developmental changes in methylation of cytosines in the proximal promoters of [[CYP3A4]] and [[CYP3A7]] in pediatric livers were confirmed by bisulfite sequencing. In addition, the methylation status of cytosine in the [[CYP3A4]] and [[CYP3A7]] proximal promoters correlated with changes in developmental expression of mRNA for the two enzymes.
|mesh-terms=* Adolescent
* Age Factors
* Aging
* Child
* Child, Preschool
* Cytochrome P-450 CYP3A
* Cytosine
* DNA Methylation
* Epigenesis, Genetic
* Female
* Gene Expression Regulation, Developmental
* Gene Expression Regulation, Enzymologic
* Gestational Age
* Humans
* Infant
* Infant, Newborn
* Liver
* Male
* Promoter Regions, Genetic
* RNA, Messenger

|full-text-url=https://sci-hub.do/10.1124/dmd.115.068726
}}
{{medline-entry
|title=Predicting the "First dose in children" of CYP3A-metabolized drugs: Evaluation of scaling approaches and insights into the [[CYP3A7]]-[[CYP3A4]] switch at young ages.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24676942
|abstract=First-dose-in-children relies on the prediction of clearance from adults for which little information is available on the accuracy of the scaling-approaches applied. For CYP3A-metabolized compounds, scaling of clearance is further challenged by different isoforms and by the [[CYP3A7]] to [[CYP3A4]] switch at young ages. This investigation aimed to evaluate the accuracy of two frequently used scaling approaches and to gain insights into the ontogeny of CYP3A. Hence, a literature database was compiled containing 203 clearance values from term-neonates to adults for 18 CYP3A-metabolized compounds. The clearances in adults were scaled to children using (i) allometric scaling plus maturation function and (ii) a mechanistic approach based on the well-stirred model. Three maturation functions were separately evaluated. In children >3 months, all approaches were interchangeable heeding the maturation function applied and biases were mostly observed in children <3 months. The results from a sensitivity analysis indicate that these biases are possibly caused by disregarding the [[CYP3A7]] activity which could account for up to 86% of the metabolism in term-neonates. Only the mechanistic approach using an overall-CYP3A maturation function led to unbiased predictions of clearances across all ages. The current investigation adds to the predictions of the first-dose-in-children of compounds (partially) metabolized by CYP3A. 
|mesh-terms=* Adolescent
* Adult
* Aging
* Algorithms
* Body Weight
* Child
* Child, Preschool
* Cytochrome P-450 CYP3A
* Hepatic Artery
* Humans
* Infant
* Infant, Newborn
* Liver
* Models, Biological
* Pharmaceutical Preparations
* Pharmacokinetics
* Portal Vein
* Regional Blood Flow
|keywords=* bridging
* children
* extrapolation
* pediatrics
* scaling
|full-text-url=https://sci-hub.do/10.1002/jcph.294
}}