New perspectives on the impact of cytochrome P450 3A expression for pediatric pharmacology
Advances in the basic and clinical sciences of drug actions and safety have been applied almost exclusively to the largest demographic patient group – adults. Metabolism-dependent drug clearance is not only a primary determinant for obtaining efficacious drug exposure, but could also demonstrate cle...
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| Veröffentlicht in: | Drug discovery today 2006-05, Vol.11 (9), p.440-445 |
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| container_title | Drug discovery today |
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| creator | Stevens, Jeffrey C. |
| description | Advances in the basic and clinical sciences of drug actions and safety have been applied almost exclusively to the largest demographic patient group – adults. Metabolism-dependent drug clearance is not only a primary determinant for obtaining efficacious drug exposure, but could also demonstrate clear age-dependence. These concepts are exemplified by the three major human cytochrome P450 (CYP) 3A enzymes: CYP3A4, CYP3A5 and CYP3A7. Recent preclinical and clinical studies show CYP3A7 is the most abundant CYP3A enzyme in fetal liver, with a gradual shift towards CYP3A4 expression throughout childhood. However, the polymorphic nature and regulatory intricacies of CYP3A5 and CYP3A7 expression could cause an underappreciated contribution to interindividual variability in drug response and safety. |
| doi_str_mv | 10.1016/j.drudis.2006.03.002 |
| format | Article |
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Metabolism-dependent drug clearance is not only a primary determinant for obtaining efficacious drug exposure, but could also demonstrate clear age-dependence. These concepts are exemplified by the three major human cytochrome P450 (CYP) 3A enzymes: CYP3A4, CYP3A5 and CYP3A7. Recent preclinical and clinical studies show CYP3A7 is the most abundant CYP3A enzyme in fetal liver, with a gradual shift towards CYP3A4 expression throughout childhood. 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Metabolism-dependent drug clearance is not only a primary determinant for obtaining efficacious drug exposure, but could also demonstrate clear age-dependence. These concepts are exemplified by the three major human cytochrome P450 (CYP) 3A enzymes: CYP3A4, CYP3A5 and CYP3A7. Recent preclinical and clinical studies show CYP3A7 is the most abundant CYP3A enzyme in fetal liver, with a gradual shift towards CYP3A4 expression throughout childhood. 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Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stevens, Jeffrey C.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Drug discovery today</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stevens, Jeffrey C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New perspectives on the impact of cytochrome P450 3A expression for pediatric pharmacology</atitle><jtitle>Drug discovery today</jtitle><addtitle>Drug Discov Today</addtitle><date>2006-05-01</date><risdate>2006</risdate><volume>11</volume><issue>9</issue><spage>440</spage><epage>445</epage><pages>440-445</pages><issn>1359-6446</issn><eissn>1878-5832</eissn><abstract>Advances in the basic and clinical sciences of drug actions and safety have been applied almost exclusively to the largest demographic patient group – adults. 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| ispartof | Drug discovery today, 2006-05, Vol.11 (9), p.440-445 |
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| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Age Factors Animals Anti-Anxiety Agents - metabolism Aryl Hydrocarbon Hydroxylases - genetics Aryl Hydrocarbon Hydroxylases - metabolism Biological and medical sciences Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Gene Expression Regulation, Developmental General pharmacology Humans Liver - enzymology Medical sciences Midazolam - metabolism Pediatrics Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology Pharmacology. Drug treatments |
| title | New perspectives on the impact of cytochrome P450 3A expression for pediatric pharmacology |
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