PHARMACOKINETICS AND SAFETY OF SINGLE INTRAVENOUS AND ORAL DOSES OF DOLASETRON MESYLATE IN HEALTHY WOMEN
Twenty‐four healthy women received 2·4 mg kg−1 dolasetron mesylate (1·8 mg kg−1 dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74 156 were monitored for 48 h in plasma. Urine was collected fr...
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| Veröffentlicht in: | Biopharmaceutics & drug disposition 1997-05, Vol.18 (4), p.361-369 |
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| creator | KEUNG, ANTHER C. F. LANDRIAULT, HÉLÈNE LEFEBVRE, MARC GOSSARD, DENIS DEMPSEY, ELLEN E. JUNEAU, MARTIN DIMMITT, DAN CASTLES, MARK ROBERTS, LISA SPÉNARD, JEAN |
| description | Twenty‐four healthy women received 2·4 mg kg−1 dolasetron mesylate (1·8 mg kg−1 dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74 156 were monitored for 48 h in plasma. Urine was collected from 0 to 48 h, blood pressure and heart rate were measured at 0, 0·08, 1, 2, 12, 24, and 36 h, and ECGs were measured at 0, 0·08 (intravenous only), 1, 2, and 36 h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t1/2=0·23 h) to MDL 74 156 (mean t1/2=8·05 and 9·12 h after intravenous and oral administration respectively). MDL 74 156 was extensively distributed; between 27 (oral route) and 33% (intravenous route) was eliminated unchanged in urine. Safety assessment showed mild to moderate headache, dizziness, and hot flushes after the intravenous administration and headache, abdominal cramps or pain, and constipation after oral administration. Small and clinically non‐significant changes in PR, QRS, and QTc intervals were observed. We conclude that there is no obvious difference in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men. ©1997 by John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/(SICI)1099-081X(199705)18:4<361::AID-BDD25>3.0.CO;2-I |
| format | Article |
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F. ; LANDRIAULT, HÉLÈNE ; LEFEBVRE, MARC ; GOSSARD, DENIS ; DEMPSEY, ELLEN E. ; JUNEAU, MARTIN ; DIMMITT, DAN ; CASTLES, MARK ; ROBERTS, LISA ; SPÉNARD, JEAN</creator><creatorcontrib>KEUNG, ANTHER C. F. ; LANDRIAULT, HÉLÈNE ; LEFEBVRE, MARC ; GOSSARD, DENIS ; DEMPSEY, ELLEN E. ; JUNEAU, MARTIN ; DIMMITT, DAN ; CASTLES, MARK ; ROBERTS, LISA ; SPÉNARD, JEAN</creatorcontrib><description>Twenty‐four healthy women received 2·4 mg kg−1 dolasetron mesylate (1·8 mg kg−1 dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74 156 were monitored for 48 h in plasma. Urine was collected from 0 to 48 h, blood pressure and heart rate were measured at 0, 0·08, 1, 2, 12, 24, and 36 h, and ECGs were measured at 0, 0·08 (intravenous only), 1, 2, and 36 h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t1/2=0·23 h) to MDL 74 156 (mean t1/2=8·05 and 9·12 h after intravenous and oral administration respectively). MDL 74 156 was extensively distributed; between 27 (oral route) and 33% (intravenous route) was eliminated unchanged in urine. Safety assessment showed mild to moderate headache, dizziness, and hot flushes after the intravenous administration and headache, abdominal cramps or pain, and constipation after oral administration. Small and clinically non‐significant changes in PR, QRS, and QTc intervals were observed. We conclude that there is no obvious difference in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men. ©1997 by John Wiley & Sons, Ltd.</description><identifier>ISSN: 0142-2782</identifier><identifier>EISSN: 1099-081X</identifier><identifier>DOI: 10.1002/(SICI)1099-081X(199705)18:4<361::AID-BDD25>3.0.CO;2-I</identifier><identifier>PMID: 9158883</identifier><identifier>CODEN: BDDID8</identifier><language>eng</language><publisher>New York: John Wiley & Sons, Ltd</publisher><subject>Administration, Oral ; Adult ; Antiemetics - administration & dosage ; Antiemetics - adverse effects ; Antiemetics - pharmacokinetics ; Biological and medical sciences ; Cross-Over Studies ; dolasetron ; Female ; Humans ; Indoles - administration & dosage ; Indoles - adverse effects ; Indoles - pharmacokinetics ; Injections, Intravenous ; intravenous ; Male ; Medical sciences ; Middle Aged ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; oral ; pharmacokinetics ; Pharmacology. Drug treatments ; Quinolizines - administration & dosage ; Quinolizines - adverse effects ; Quinolizines - pharmacokinetics ; Serotonin Antagonists - administration & dosage ; Serotonin Antagonists - adverse effects ; Serotonin Antagonists - pharmacokinetics ; Serotoninergic system ; Sex Factors ; women</subject><ispartof>Biopharmaceutics & drug disposition, 1997-05, Vol.18 (4), p.361-369</ispartof><rights>Copyright © 1997 John Wiley & Sons, Ltd.</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F%28SICI%291099-081X%28199705%2918%3A4%3C361%3A%3AAID-BDD25%3E3.0.CO%3B2-I$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F%28SICI%291099-081X%28199705%2918%3A4%3C361%3A%3AAID-BDD25%3E3.0.CO%3B2-I$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2674126$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9158883$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KEUNG, ANTHER C. F.</creatorcontrib><creatorcontrib>LANDRIAULT, HÉLÈNE</creatorcontrib><creatorcontrib>LEFEBVRE, MARC</creatorcontrib><creatorcontrib>GOSSARD, DENIS</creatorcontrib><creatorcontrib>DEMPSEY, ELLEN E.</creatorcontrib><creatorcontrib>JUNEAU, MARTIN</creatorcontrib><creatorcontrib>DIMMITT, DAN</creatorcontrib><creatorcontrib>CASTLES, MARK</creatorcontrib><creatorcontrib>ROBERTS, LISA</creatorcontrib><creatorcontrib>SPÉNARD, JEAN</creatorcontrib><title>PHARMACOKINETICS AND SAFETY OF SINGLE INTRAVENOUS AND ORAL DOSES OF DOLASETRON MESYLATE IN HEALTHY WOMEN</title><title>Biopharmaceutics & drug disposition</title><addtitle>Biopharm. Drug Dispos</addtitle><description>Twenty‐four healthy women received 2·4 mg kg−1 dolasetron mesylate (1·8 mg kg−1 dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74 156 were monitored for 48 h in plasma. Urine was collected from 0 to 48 h, blood pressure and heart rate were measured at 0, 0·08, 1, 2, 12, 24, and 36 h, and ECGs were measured at 0, 0·08 (intravenous only), 1, 2, and 36 h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t1/2=0·23 h) to MDL 74 156 (mean t1/2=8·05 and 9·12 h after intravenous and oral administration respectively). MDL 74 156 was extensively distributed; between 27 (oral route) and 33% (intravenous route) was eliminated unchanged in urine. Safety assessment showed mild to moderate headache, dizziness, and hot flushes after the intravenous administration and headache, abdominal cramps or pain, and constipation after oral administration. Small and clinically non‐significant changes in PR, QRS, and QTc intervals were observed. We conclude that there is no obvious difference in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men. ©1997 by John Wiley & Sons, Ltd.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Antiemetics - administration & dosage</subject><subject>Antiemetics - adverse effects</subject><subject>Antiemetics - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Cross-Over Studies</subject><subject>dolasetron</subject><subject>Female</subject><subject>Humans</subject><subject>Indoles - administration & dosage</subject><subject>Indoles - adverse effects</subject><subject>Indoles - pharmacokinetics</subject><subject>Injections, Intravenous</subject><subject>intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>oral</subject><subject>pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Quinolizines - administration & dosage</subject><subject>Quinolizines - adverse effects</subject><subject>Quinolizines - pharmacokinetics</subject><subject>Serotonin Antagonists - administration & dosage</subject><subject>Serotonin Antagonists - adverse effects</subject><subject>Serotonin Antagonists - pharmacokinetics</subject><subject>Serotoninergic system</subject><subject>Sex Factors</subject><subject>women</subject><issn>0142-2782</issn><issn>1099-081X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVtv00AQhS0EKqXwE5D8gFD74DB7s9fhIi22m1g4XhS7CenLyHZtEUia4m0E_ffYOMoLSDytNHPm7NH5LOs9gREBoG_OsziILwj4vgOSfDknvu-BuCByzN8xl4zHKg6dj2FIxQc2glGg31InfmSdHi8eW6dAOHWoJ-lT65kx3wDAJYScWCc-EVJKdmp9_TxV85kK9Kc4jfI4yGyVhnamLqN8ZetLO4vTSRLZcZrP1SJK9dUg0HOV2KHOoqwXhTpRWZTPdWrPomyVqLy_sKeRSvLpyl7qWZQ-t540xcbULw7vmXXV_RFMnURP4kAlTsVdIpwSZOMTIkoBFQPOZMOoC9xr2A0XooKC0gZICXVT-tRvaNmNXGC0ENzjHvPYmfV68L1rdz_2tbnH7dpU9WZT3Na7vUEifO5RBuwYoGp3xrR1g3ftelu0D0gAewKIPQHs-8S-TxwIIJHIsSOA2BHAPwSQIWCgkWLc-b48BNiX2_rm6HqovNu_OuwLUxWbpi1uq7U5yqjrcULdTrYYZD_Xm_rhr2z_ifavZMOgM3YG47W5r38djYv2O7pdgQKX6QRncjGVS36N1-w3JfyyLw</recordid><startdate>199705</startdate><enddate>199705</enddate><creator>KEUNG, ANTHER C. F.</creator><creator>LANDRIAULT, HÉLÈNE</creator><creator>LEFEBVRE, MARC</creator><creator>GOSSARD, DENIS</creator><creator>DEMPSEY, ELLEN E.</creator><creator>JUNEAU, MARTIN</creator><creator>DIMMITT, DAN</creator><creator>CASTLES, MARK</creator><creator>ROBERTS, LISA</creator><creator>SPÉNARD, JEAN</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>BSCLL</scope><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>7T2</scope><scope>7U2</scope><scope>C1K</scope></search><sort><creationdate>199705</creationdate><title>PHARMACOKINETICS AND SAFETY OF SINGLE INTRAVENOUS AND ORAL DOSES OF DOLASETRON MESYLATE IN HEALTHY WOMEN</title><author>KEUNG, ANTHER C. F. ; LANDRIAULT, HÉLÈNE ; LEFEBVRE, MARC ; GOSSARD, DENIS ; DEMPSEY, ELLEN E. ; JUNEAU, MARTIN ; DIMMITT, DAN ; CASTLES, MARK ; ROBERTS, LISA ; SPÉNARD, JEAN</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4615-b08f9115b50c30438f326047f3d455c0a22f01b0efb929f2bc0a6032a54747373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Administration, Oral</topic><topic>Adult</topic><topic>Antiemetics - administration & dosage</topic><topic>Antiemetics - adverse effects</topic><topic>Antiemetics - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Cross-Over Studies</topic><topic>dolasetron</topic><topic>Female</topic><topic>Humans</topic><topic>Indoles - administration & dosage</topic><topic>Indoles - adverse effects</topic><topic>Indoles - pharmacokinetics</topic><topic>Injections, Intravenous</topic><topic>intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>oral</topic><topic>pharmacokinetics</topic><topic>Pharmacology. Drug treatments</topic><topic>Quinolizines - administration & dosage</topic><topic>Quinolizines - adverse effects</topic><topic>Quinolizines - pharmacokinetics</topic><topic>Serotonin Antagonists - administration & dosage</topic><topic>Serotonin Antagonists - adverse effects</topic><topic>Serotonin Antagonists - pharmacokinetics</topic><topic>Serotoninergic system</topic><topic>Sex Factors</topic><topic>women</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KEUNG, ANTHER C. F.</creatorcontrib><creatorcontrib>LANDRIAULT, HÉLÈNE</creatorcontrib><creatorcontrib>LEFEBVRE, MARC</creatorcontrib><creatorcontrib>GOSSARD, DENIS</creatorcontrib><creatorcontrib>DEMPSEY, ELLEN E.</creatorcontrib><creatorcontrib>JUNEAU, MARTIN</creatorcontrib><creatorcontrib>DIMMITT, DAN</creatorcontrib><creatorcontrib>CASTLES, MARK</creatorcontrib><creatorcontrib>ROBERTS, LISA</creatorcontrib><creatorcontrib>SPÉNARD, JEAN</creatorcontrib><collection>Istex</collection><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>Health and Safety Science Abstracts (Full archive)</collection><collection>Safety Science and Risk</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Biopharmaceutics & drug disposition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KEUNG, ANTHER C. F.</au><au>LANDRIAULT, HÉLÈNE</au><au>LEFEBVRE, MARC</au><au>GOSSARD, DENIS</au><au>DEMPSEY, ELLEN E.</au><au>JUNEAU, MARTIN</au><au>DIMMITT, DAN</au><au>CASTLES, MARK</au><au>ROBERTS, LISA</au><au>SPÉNARD, JEAN</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PHARMACOKINETICS AND SAFETY OF SINGLE INTRAVENOUS AND ORAL DOSES OF DOLASETRON MESYLATE IN HEALTHY WOMEN</atitle><jtitle>Biopharmaceutics & drug disposition</jtitle><addtitle>Biopharm. Drug Dispos</addtitle><date>1997-05</date><risdate>1997</risdate><volume>18</volume><issue>4</issue><spage>361</spage><epage>369</epage><pages>361-369</pages><issn>0142-2782</issn><eissn>1099-081X</eissn><coden>BDDID8</coden><abstract>Twenty‐four healthy women received 2·4 mg kg−1 dolasetron mesylate (1·8 mg kg−1 dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74 156 were monitored for 48 h in plasma. Urine was collected from 0 to 48 h, blood pressure and heart rate were measured at 0, 0·08, 1, 2, 12, 24, and 36 h, and ECGs were measured at 0, 0·08 (intravenous only), 1, 2, and 36 h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t1/2=0·23 h) to MDL 74 156 (mean t1/2=8·05 and 9·12 h after intravenous and oral administration respectively). MDL 74 156 was extensively distributed; between 27 (oral route) and 33% (intravenous route) was eliminated unchanged in urine. Safety assessment showed mild to moderate headache, dizziness, and hot flushes after the intravenous administration and headache, abdominal cramps or pain, and constipation after oral administration. Small and clinically non‐significant changes in PR, QRS, and QTc intervals were observed. We conclude that there is no obvious difference in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men. ©1997 by John Wiley & Sons, Ltd.</abstract><cop>New York</cop><pub>John Wiley & Sons, Ltd</pub><pmid>9158883</pmid><doi>10.1002/(SICI)1099-081X(199705)18:4<361::AID-BDD25>3.0.CO;2-I</doi><tpages>9</tpages></addata></record> |
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| subjects | Administration, Oral Adult Antiemetics - administration & dosage Antiemetics - adverse effects Antiemetics - pharmacokinetics Biological and medical sciences Cross-Over Studies dolasetron Female Humans Indoles - administration & dosage Indoles - adverse effects Indoles - pharmacokinetics Injections, Intravenous intravenous Male Medical sciences Middle Aged Neuropharmacology Neurotransmitters. Neurotransmission. Receptors oral pharmacokinetics Pharmacology. Drug treatments Quinolizines - administration & dosage Quinolizines - adverse effects Quinolizines - pharmacokinetics Serotonin Antagonists - administration & dosage Serotonin Antagonists - adverse effects Serotonin Antagonists - pharmacokinetics Serotoninergic system Sex Factors women |
| title | PHARMACOKINETICS AND SAFETY OF SINGLE INTRAVENOUS AND ORAL DOSES OF DOLASETRON MESYLATE IN HEALTHY WOMEN |
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