Stimulatory as well as inhibitory effects of ethinyloestradiol on the metabolic clearances of propranolol in young women
1 The metabolism of a single 80 mg oral dose of propranolol was determined in nine young women before and after administration of ethinyloestradiol alone (EE2) or in combination with norethindrone (OC). 2 Whereas the total clearance of propranolol (2713±404 ml min−1 (mean±s.e.mean)) was not signific...
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| Veröffentlicht in: | British journal of clinical pharmacology 1996-04, Vol.41 (4), p.305-309 |
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| creator | WALLE, T. FAGAN, T. C. WALLE, U. K. TOPMILLER, M. J. |
| description | 1 The metabolism of a single 80 mg oral dose of propranolol was determined in nine young women before and after administration of ethinyloestradiol alone (EE2) or in combination with norethindrone (OC).
2 Whereas the total clearance of propranolol (2713±404 ml min−1 (mean±s.e.mean)) was not significantly altered by either EE2 (3365±347 ml min−1) or the combined OC (2905±345 ml min−1), significant changes in all three primary metabolic pathways were observed.
3 The clearance through side‐chain oxidation decreased from 345±55 ml min−1 to 262±33 ml min−1 after EE2 (P |
| doi_str_mv | 10.1046/j.1365-2125.1996.03097.x |
| format | Article |
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2 Whereas the total clearance of propranolol (2713±404 ml min−1 (mean±s.e.mean)) was not significantly altered by either EE2 (3365±347 ml min−1) or the combined OC (2905±345 ml min−1), significant changes in all three primary metabolic pathways were observed.
3 The clearance through side‐chain oxidation decreased from 345±55 ml min−1 to 262±33 ml min−1 after EE2 (P<0.05). A similar reduction of cytochrome P450 metabolism by EE2 has been observed for other drugs.
4 The clearance through glucuronidation increased from 364±61 ml min−1 to 625±117 ml min−1 after EE2 (P<0.01). Similar stimulation of glucuronic acid conjugation by EE2 has also been observed for other drugs.
5 The clearance through ring oxidation increased from 697±109 ml min−1 to 1280±162 ml min−1 after EE2 (P<0.01). This observation appears to be a novel finding with EE2 and cytochrome P450 metabolism.
6 The treatment with OC produced changes in propranolol's metabolic clearances which were qualitatively similar to those generated by EE2.</description><identifier>ISSN: 0306-5251</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1046/j.1365-2125.1996.03097.x</identifier><identifier>PMID: 8730976</identifier><language>eng</language><publisher>Oxford: Blackwell Science Ltd</publisher><subject>Adrenergic beta-Agonists - blood ; Adrenergic beta-Agonists - metabolism ; Adult ; Contraceptives, Oral, Combined - pharmacology ; Contraceptives, Oral, Synthetic - pharmacology ; Estradiol Congeners - pharmacology ; Ethinyl Estradiol - pharmacology ; ethinyloestradiol ; Female ; Humans ; metabolism ; Norethindrone - pharmacology ; oral contraceptives ; Original ; propranolol ; Propranolol - blood ; Propranolol - metabolism ; women</subject><ispartof>British journal of clinical pharmacology, 1996-04, Vol.41 (4), p.305-309</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4929-50a3e6b8de5ac460c5bfafe95f3b9b73e177abc08d2f011854cfa332d0513cc13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8730976$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WALLE, T.</creatorcontrib><creatorcontrib>FAGAN, T. C.</creatorcontrib><creatorcontrib>WALLE, U. K.</creatorcontrib><creatorcontrib>TOPMILLER, M. J.</creatorcontrib><title>Stimulatory as well as inhibitory effects of ethinyloestradiol on the metabolic clearances of propranolol in young women</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>1 The metabolism of a single 80 mg oral dose of propranolol was determined in nine young women before and after administration of ethinyloestradiol alone (EE2) or in combination with norethindrone (OC).
2 Whereas the total clearance of propranolol (2713±404 ml min−1 (mean±s.e.mean)) was not significantly altered by either EE2 (3365±347 ml min−1) or the combined OC (2905±345 ml min−1), significant changes in all three primary metabolic pathways were observed.
3 The clearance through side‐chain oxidation decreased from 345±55 ml min−1 to 262±33 ml min−1 after EE2 (P<0.05). A similar reduction of cytochrome P450 metabolism by EE2 has been observed for other drugs.
4 The clearance through glucuronidation increased from 364±61 ml min−1 to 625±117 ml min−1 after EE2 (P<0.01). Similar stimulation of glucuronic acid conjugation by EE2 has also been observed for other drugs.
5 The clearance through ring oxidation increased from 697±109 ml min−1 to 1280±162 ml min−1 after EE2 (P<0.01). This observation appears to be a novel finding with EE2 and cytochrome P450 metabolism.
6 The treatment with OC produced changes in propranolol's metabolic clearances which were qualitatively similar to those generated by EE2.</description><subject>Adrenergic beta-Agonists - blood</subject><subject>Adrenergic beta-Agonists - metabolism</subject><subject>Adult</subject><subject>Contraceptives, Oral, Combined - pharmacology</subject><subject>Contraceptives, Oral, Synthetic - pharmacology</subject><subject>Estradiol Congeners - pharmacology</subject><subject>Ethinyl Estradiol - pharmacology</subject><subject>ethinyloestradiol</subject><subject>Female</subject><subject>Humans</subject><subject>metabolism</subject><subject>Norethindrone - pharmacology</subject><subject>oral contraceptives</subject><subject>Original</subject><subject>propranolol</subject><subject>Propranolol - blood</subject><subject>Propranolol - metabolism</subject><subject>women</subject><issn>0306-5251</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUU2P0zAQtRBo6S78BCSfuCVrx7GTSAgJKnZBWgmkXc6W44y3rhy7xAlt_j1OW1Vw4zT2vI8Z-yGEKckpKcXtNqdM8KygBc9p04icMNJU-eEFWl2Al2iVuiLjBaev0XWMW0Ioo4Jfoau6WvhihQ6Po-0np8YwzFhFvAfnlmr9xrb22AVjQI8RB4Nh3Fg_uwBxHFRng8PB43EDuIdRtcFZjbUDNSiv4SjYDWGXbsElqvV4DpN_xvvQg3-DXhnlIrw91xv08-7L0_pr9vD9_tv600Omy6ZoMk4UA9HWHXClS0E0b40y0HDD2qatGNCqUq0mdVcYQmnNS20UY0VHOGVaU3aDPp58d1PbQ6fBp9Wd3A22V8Msg7LyX8TbjXwOv2VByoI3LBm8PxsM4deUXi57G3X6JuUhTFFWNRVCFGUi1ieiHkKMA5jLEErkkprcyiUcuYQjl9TkMTV5SNJ3fy95EZ5jSviHE763Dub_9pWf1z_Sif0BbPiqwQ</recordid><startdate>199604</startdate><enddate>199604</enddate><creator>WALLE, T.</creator><creator>FAGAN, T. C.</creator><creator>WALLE, U. K.</creator><creator>TOPMILLER, M. J.</creator><general>Blackwell Science Ltd</general><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><scope>5PM</scope></search><sort><creationdate>199604</creationdate><title>Stimulatory as well as inhibitory effects of ethinyloestradiol on the metabolic clearances of propranolol in young women</title><author>WALLE, T. ; FAGAN, T. C. ; WALLE, U. K. ; TOPMILLER, M. J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4929-50a3e6b8de5ac460c5bfafe95f3b9b73e177abc08d2f011854cfa332d0513cc13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adrenergic beta-Agonists - blood</topic><topic>Adrenergic beta-Agonists - metabolism</topic><topic>Adult</topic><topic>Contraceptives, Oral, Combined - pharmacology</topic><topic>Contraceptives, Oral, Synthetic - pharmacology</topic><topic>Estradiol Congeners - pharmacology</topic><topic>Ethinyl Estradiol - pharmacology</topic><topic>ethinyloestradiol</topic><topic>Female</topic><topic>Humans</topic><topic>metabolism</topic><topic>Norethindrone - pharmacology</topic><topic>oral contraceptives</topic><topic>Original</topic><topic>propranolol</topic><topic>Propranolol - blood</topic><topic>Propranolol - metabolism</topic><topic>women</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WALLE, T.</creatorcontrib><creatorcontrib>FAGAN, T. C.</creatorcontrib><creatorcontrib>WALLE, U. K.</creatorcontrib><creatorcontrib>TOPMILLER, M. J.</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WALLE, T.</au><au>FAGAN, T. C.</au><au>WALLE, U. K.</au><au>TOPMILLER, M. J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stimulatory as well as inhibitory effects of ethinyloestradiol on the metabolic clearances of propranolol in young women</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>1996-04</date><risdate>1996</risdate><volume>41</volume><issue>4</issue><spage>305</spage><epage>309</epage><pages>305-309</pages><issn>0306-5251</issn><eissn>1365-2125</eissn><abstract>1 The metabolism of a single 80 mg oral dose of propranolol was determined in nine young women before and after administration of ethinyloestradiol alone (EE2) or in combination with norethindrone (OC).
2 Whereas the total clearance of propranolol (2713±404 ml min−1 (mean±s.e.mean)) was not significantly altered by either EE2 (3365±347 ml min−1) or the combined OC (2905±345 ml min−1), significant changes in all three primary metabolic pathways were observed.
3 The clearance through side‐chain oxidation decreased from 345±55 ml min−1 to 262±33 ml min−1 after EE2 (P<0.05). A similar reduction of cytochrome P450 metabolism by EE2 has been observed for other drugs.
4 The clearance through glucuronidation increased from 364±61 ml min−1 to 625±117 ml min−1 after EE2 (P<0.01). Similar stimulation of glucuronic acid conjugation by EE2 has also been observed for other drugs.
5 The clearance through ring oxidation increased from 697±109 ml min−1 to 1280±162 ml min−1 after EE2 (P<0.01). This observation appears to be a novel finding with EE2 and cytochrome P450 metabolism.
6 The treatment with OC produced changes in propranolol's metabolic clearances which were qualitatively similar to those generated by EE2.</abstract><cop>Oxford</cop><pub>Blackwell Science Ltd</pub><pmid>8730976</pmid><doi>10.1046/j.1365-2125.1996.03097.x</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adrenergic beta-Agonists - blood Adrenergic beta-Agonists - metabolism Adult Contraceptives, Oral, Combined - pharmacology Contraceptives, Oral, Synthetic - pharmacology Estradiol Congeners - pharmacology Ethinyl Estradiol - pharmacology ethinyloestradiol Female Humans metabolism Norethindrone - pharmacology oral contraceptives Original propranolol Propranolol - blood Propranolol - metabolism women |
| title | Stimulatory as well as inhibitory effects of ethinyloestradiol on the metabolic clearances of propranolol in young women |
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