Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy
The purpose of this study was to determine whether drug metabolism (CYP1A2, CYP2D6 and CYP3A) activity varies in the pregnant state compared with the nonpregnant state. Subjects were studied at 14 to18 weeks of gestation, 24 to 28 weeks of gestation, and 36 to 40 weeks of gestation and again at 6 to...
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| Veröffentlicht in: | American journal of obstetrics and gynecology 2005-02, Vol.192 (2), p.633-639 |
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| container_title | American journal of obstetrics and gynecology |
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| creator | Tracy, Timothy S. Venkataramanan, Raman Glover, Douglas D. Caritis, Steve N. |
| description | The purpose of this study was to determine whether drug metabolism (CYP1A2, CYP2D6 and CYP3A) activity varies in the pregnant state compared with the nonpregnant state.
Subjects were studied at 14 to18 weeks of gestation, 24 to 28 weeks of gestation, and 36 to 40 weeks of gestation and again at 6 to 8 weeks after the delivery. Twenty-five subjects completed all 4 study periods and had evaluable data. Salivary caffeine clearance was used as a measure of CYP1A2 activity; dextromethorphan O- and N-demethylation were used to assess CYP2D6 and CYP3A activity, respectively.
CYP1A2 activity was significantly reduced at all periods of the pregnancy as compared with the postpartum period during the first (−32.8% ± 22.8%), second (−48.1% ± 27%), and third periods (−65.2% ± 15.3%), respectively. In contrast, CYP2D6 activity was increased significantly throughout the pregnancy (25.6% ± 58.3% at 14-18 weeks of gestation, 34.8% ± 41.4% at 24-28 weeks of gestation, and 47.8% ± 24.7% at 36-40 weeks of gestation) as compared with the postpartum period. CYP3A activity was consistently, significantly increased (35%-38%) during all stages of the pregnancy.
Opposing changes in drug metabolism occur during pregnancy, with CYP1A2 activity decreased and CYP2D6 and CYP3A activities increased. The direction of dosing adjustments during pregnancy will depend on the drug and the enzyme that is responsible for its metabolism. |
| doi_str_mv | 10.1016/j.ajog.2004.08.030 |
| format | Article |
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Subjects were studied at 14 to18 weeks of gestation, 24 to 28 weeks of gestation, and 36 to 40 weeks of gestation and again at 6 to 8 weeks after the delivery. Twenty-five subjects completed all 4 study periods and had evaluable data. Salivary caffeine clearance was used as a measure of CYP1A2 activity; dextromethorphan O- and N-demethylation were used to assess CYP2D6 and CYP3A activity, respectively.
CYP1A2 activity was significantly reduced at all periods of the pregnancy as compared with the postpartum period during the first (−32.8% ± 22.8%), second (−48.1% ± 27%), and third periods (−65.2% ± 15.3%), respectively. In contrast, CYP2D6 activity was increased significantly throughout the pregnancy (25.6% ± 58.3% at 14-18 weeks of gestation, 34.8% ± 41.4% at 24-28 weeks of gestation, and 47.8% ± 24.7% at 36-40 weeks of gestation) as compared with the postpartum period. CYP3A activity was consistently, significantly increased (35%-38%) during all stages of the pregnancy.
Opposing changes in drug metabolism occur during pregnancy, with CYP1A2 activity decreased and CYP2D6 and CYP3A activities increased. The direction of dosing adjustments during pregnancy will depend on the drug and the enzyme that is responsible for its metabolism.</description><identifier>ISSN: 0002-9378</identifier><identifier>EISSN: 1097-6868</identifier><identifier>DOI: 10.1016/j.ajog.2004.08.030</identifier><identifier>PMID: 15696014</identifier><identifier>CODEN: AJOGAH</identifier><language>eng</language><publisher>Philadelphia, PA: Mosby, Inc</publisher><subject>Adolescent ; Adult ; Aryl Hydrocarbon Hydroxylases - metabolism ; Biological and medical sciences ; Caffeine - metabolism ; Cytochrome P-450 CYP1A2 - metabolism ; Cytochrome P-450 CYP2D6 - metabolism ; Cytochrome P-450 CYP3A ; Cytochrome P450 ; Dextromethorphan - analogs & derivatives ; Dextromethorphan - metabolism ; Drug metabolism ; Female ; Gynecology. Andrology. Obstetrics ; Humans ; Medical sciences ; Oxidoreductases, N-Demethylating - metabolism ; Pregnancy ; Pregnancy - metabolism</subject><ispartof>American journal of obstetrics and gynecology, 2005-02, Vol.192 (2), p.633-639</ispartof><rights>2005 Elsevier Inc.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-7eb543d4587cf7161dece2f6ad7f9f89fc43ec786986883934e9979d821c01033</citedby><cites>FETCH-LOGICAL-c475t-7eb543d4587cf7161dece2f6ad7f9f89fc43ec786986883934e9979d821c01033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002937804009597$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16524595$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15696014$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tracy, Timothy S.</creatorcontrib><creatorcontrib>Venkataramanan, Raman</creatorcontrib><creatorcontrib>Glover, Douglas D.</creatorcontrib><creatorcontrib>Caritis, Steve N.</creatorcontrib><creatorcontrib>for the National Institute for Child Health and Human Development Network of Maternal-Fetal-Medicine Units</creatorcontrib><creatorcontrib>National Institute for Child Health and Human Development Network of Maternal-Fetal-Medicine Units</creatorcontrib><title>Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy</title><title>American journal of obstetrics and gynecology</title><addtitle>Am J Obstet Gynecol</addtitle><description>The purpose of this study was to determine whether drug metabolism (CYP1A2, CYP2D6 and CYP3A) activity varies in the pregnant state compared with the nonpregnant state.
Subjects were studied at 14 to18 weeks of gestation, 24 to 28 weeks of gestation, and 36 to 40 weeks of gestation and again at 6 to 8 weeks after the delivery. Twenty-five subjects completed all 4 study periods and had evaluable data. Salivary caffeine clearance was used as a measure of CYP1A2 activity; dextromethorphan O- and N-demethylation were used to assess CYP2D6 and CYP3A activity, respectively.
CYP1A2 activity was significantly reduced at all periods of the pregnancy as compared with the postpartum period during the first (−32.8% ± 22.8%), second (−48.1% ± 27%), and third periods (−65.2% ± 15.3%), respectively. In contrast, CYP2D6 activity was increased significantly throughout the pregnancy (25.6% ± 58.3% at 14-18 weeks of gestation, 34.8% ± 41.4% at 24-28 weeks of gestation, and 47.8% ± 24.7% at 36-40 weeks of gestation) as compared with the postpartum period. CYP3A activity was consistently, significantly increased (35%-38%) during all stages of the pregnancy.
Opposing changes in drug metabolism occur during pregnancy, with CYP1A2 activity decreased and CYP2D6 and CYP3A activities increased. The direction of dosing adjustments during pregnancy will depend on the drug and the enzyme that is responsible for its metabolism.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aryl Hydrocarbon Hydroxylases - metabolism</subject><subject>Biological and medical sciences</subject><subject>Caffeine - metabolism</subject><subject>Cytochrome P-450 CYP1A2 - metabolism</subject><subject>Cytochrome P-450 CYP2D6 - metabolism</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Cytochrome P450</subject><subject>Dextromethorphan - analogs & derivatives</subject><subject>Dextromethorphan - metabolism</subject><subject>Drug metabolism</subject><subject>Female</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Oxidoreductases, N-Demethylating - metabolism</subject><subject>Pregnancy</subject><subject>Pregnancy - metabolism</subject><issn>0002-9378</issn><issn>1097-6868</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMuLFDEQh4Mo7rj6D3iQXBQFu82r8wAvw_iEBT2soKeQSarbDP2YTboX5r83zQzszVNVwVdF_T6EXlJSU0Llh0PtDlNXM0JETXRNOHmENpQYVUkt9WO0IYSwynClr9CznA_ryAx7iq5oI40kVGzQ71sYjlNyPfZ_3dhBxnHEIS0dHmB2-6mPecBvd39-0i17j0tlnyR2Y1hbvsVbP8f7OJ_e4bCkOHb4mKAb3ehPz9GT1vUZXlzqNfr15fPt7lt18-Pr9932pvJCNXOlYN8IHkSjlW8VlTSAB9ZKF1RrWm1aLzh4paUpkTQ3XIAxygTNqCeUcH6N3pzvHtN0t0Ce7RCzh753I0xLtlIJolnDCsjOoE9Tzglae0xxcOlkKbGrT3uwq0-7-rRE2-KzLL26XF_2A4SHlYvAAry-AC5717epZI_5gZMNE41pCvfxzEFxcR8h2ewjjB5CTOBnG6b4vz_-AQeRkKc</recordid><startdate>20050201</startdate><enddate>20050201</enddate><creator>Tracy, Timothy S.</creator><creator>Venkataramanan, Raman</creator><creator>Glover, Douglas D.</creator><creator>Caritis, Steve N.</creator><general>Mosby, Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20050201</creationdate><title>Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy</title><author>Tracy, Timothy S. ; Venkataramanan, Raman ; Glover, Douglas D. ; Caritis, Steve N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-7eb543d4587cf7161dece2f6ad7f9f89fc43ec786986883934e9979d821c01033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aryl Hydrocarbon Hydroxylases - metabolism</topic><topic>Biological and medical sciences</topic><topic>Caffeine - metabolism</topic><topic>Cytochrome P-450 CYP1A2 - metabolism</topic><topic>Cytochrome P-450 CYP2D6 - metabolism</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Cytochrome P450</topic><topic>Dextromethorphan - analogs & derivatives</topic><topic>Dextromethorphan - metabolism</topic><topic>Drug metabolism</topic><topic>Female</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Oxidoreductases, N-Demethylating - metabolism</topic><topic>Pregnancy</topic><topic>Pregnancy - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tracy, Timothy S.</creatorcontrib><creatorcontrib>Venkataramanan, Raman</creatorcontrib><creatorcontrib>Glover, Douglas D.</creatorcontrib><creatorcontrib>Caritis, Steve N.</creatorcontrib><creatorcontrib>for the National Institute for Child Health and Human Development Network of Maternal-Fetal-Medicine Units</creatorcontrib><creatorcontrib>National Institute for Child Health and Human Development Network of Maternal-Fetal-Medicine Units</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>American journal of obstetrics and gynecology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tracy, Timothy S.</au><au>Venkataramanan, Raman</au><au>Glover, Douglas D.</au><au>Caritis, Steve N.</au><aucorp>for the National Institute for Child Health and Human Development Network of Maternal-Fetal-Medicine Units</aucorp><aucorp>National Institute for Child Health and Human Development Network of Maternal-Fetal-Medicine Units</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy</atitle><jtitle>American journal of obstetrics and gynecology</jtitle><addtitle>Am J Obstet Gynecol</addtitle><date>2005-02-01</date><risdate>2005</risdate><volume>192</volume><issue>2</issue><spage>633</spage><epage>639</epage><pages>633-639</pages><issn>0002-9378</issn><eissn>1097-6868</eissn><coden>AJOGAH</coden><abstract>The purpose of this study was to determine whether drug metabolism (CYP1A2, CYP2D6 and CYP3A) activity varies in the pregnant state compared with the nonpregnant state.
Subjects were studied at 14 to18 weeks of gestation, 24 to 28 weeks of gestation, and 36 to 40 weeks of gestation and again at 6 to 8 weeks after the delivery. Twenty-five subjects completed all 4 study periods and had evaluable data. Salivary caffeine clearance was used as a measure of CYP1A2 activity; dextromethorphan O- and N-demethylation were used to assess CYP2D6 and CYP3A activity, respectively.
CYP1A2 activity was significantly reduced at all periods of the pregnancy as compared with the postpartum period during the first (−32.8% ± 22.8%), second (−48.1% ± 27%), and third periods (−65.2% ± 15.3%), respectively. In contrast, CYP2D6 activity was increased significantly throughout the pregnancy (25.6% ± 58.3% at 14-18 weeks of gestation, 34.8% ± 41.4% at 24-28 weeks of gestation, and 47.8% ± 24.7% at 36-40 weeks of gestation) as compared with the postpartum period. CYP3A activity was consistently, significantly increased (35%-38%) during all stages of the pregnancy.
Opposing changes in drug metabolism occur during pregnancy, with CYP1A2 activity decreased and CYP2D6 and CYP3A activities increased. The direction of dosing adjustments during pregnancy will depend on the drug and the enzyme that is responsible for its metabolism.</abstract><cop>Philadelphia, PA</cop><pub>Mosby, Inc</pub><pmid>15696014</pmid><doi>10.1016/j.ajog.2004.08.030</doi><tpages>7</tpages></addata></record> |
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| identifier | ISSN: 0002-9378 |
| ispartof | American journal of obstetrics and gynecology, 2005-02, Vol.192 (2), p.633-639 |
| issn | 0002-9378 1097-6868 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adolescent Adult Aryl Hydrocarbon Hydroxylases - metabolism Biological and medical sciences Caffeine - metabolism Cytochrome P-450 CYP1A2 - metabolism Cytochrome P-450 CYP2D6 - metabolism Cytochrome P-450 CYP3A Cytochrome P450 Dextromethorphan - analogs & derivatives Dextromethorphan - metabolism Drug metabolism Female Gynecology. Andrology. Obstetrics Humans Medical sciences Oxidoreductases, N-Demethylating - metabolism Pregnancy Pregnancy - metabolism |
| title | Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy |
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