The interaction of the diltiazem with oral and intravenous cyclosporine in rats
This study investigated the effect of diltiazem on the bioavailability of oral and intravenous cyclosporine (CsA) in rats. While control rats received normal saline, experimental groups received 60 or 90 mg/kg diltiazem orally for 3 days. Each group divided into 2 equal groups that received a single...
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| Veröffentlicht in: | European journal of drug metabolism and pharmacokinetics 2004-04, Vol.29 (2), p.119-123 |
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| container_title | European journal of drug metabolism and pharmacokinetics |
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| creator | KALKAN, Sule GUMUSTEKIN, Mukaddes AYGOREN, Oguz TUNCOK, Yesim GELAL, Ayse GUVEN, Hulya |
| description | This study investigated the effect of diltiazem on the bioavailability of oral and intravenous cyclosporine (CsA) in rats. While control rats received normal saline, experimental groups received 60 or 90 mg/kg diltiazem orally for 3 days. Each group divided into 2 equal groups that received a single oral dose or i.v. injection of CsA. Pharmacokinetic parameters were analyzed by nonparametric analysis of variance. Pretreatment with 60 or 90 mg/kg diltiazem decreased the area under the blood CsA concentration-time curve (AUC) of oral CsA compared to control group (54.5% and 65.5% for AUC(0-24), 57.6% and 62.2% for AUC(0-infinity), respectively, p |
| doi_str_mv | 10.1007/BF03190586 |
| format | Article |
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While control rats received normal saline, experimental groups received 60 or 90 mg/kg diltiazem orally for 3 days. Each group divided into 2 equal groups that received a single oral dose or i.v. injection of CsA. Pharmacokinetic parameters were analyzed by nonparametric analysis of variance. Pretreatment with 60 or 90 mg/kg diltiazem decreased the area under the blood CsA concentration-time curve (AUC) of oral CsA compared to control group (54.5% and 65.5% for AUC(0-24), 57.6% and 62.2% for AUC(0-infinity), respectively, p<0.05). Mean CsA maximum concentration (Cmax) decreased from 0.4 +/- 0.1 microg/ml to 0.1 +/- 0.0 microg/mL in rats pretreated with 90 mg/kg diltiazem (p<0.05). The absolute bioavailability after oral administration (F(p.o.)) in the 60 or 90 mg/kg diltiazem groups were lower than the control group (9.6% and 8.5% versus 22.6%). Pretreatment with 90 mg/kg but not 60 mg/kg of diltiazem increased the AUC(0-infinity), elimination half-life (t1/2) of intravenous CsA (116.0%, 219.2%, respectively, p<0.05) and decreased the intravenous CsA clearence (CL(i.v.)) (62.9%, p<0.05). Diltiazem decreased the bioavailability of oral CsA, while it increased the bioavailability of intravenous CsA. One must consider this interaction when administering oral or intravenous CsA concomitantly with diltiazem.</description><identifier>ISSN: 0378-7966</identifier><identifier>EISSN: 2107-0180</identifier><identifier>DOI: 10.1007/BF03190586</identifier><identifier>PMID: 15230340</identifier><language>eng</language><publisher>Genève: Médecine et hygiène</publisher><subject>Administration, Oral ; Animals ; Antihypertensive agents ; Area Under Curve ; Biological and medical sciences ; Calcium Channel Blockers - pharmacology ; Cardiovascular system ; Cyclosporine - pharmacokinetics ; Diltiazem - pharmacology ; Drug Interactions ; Immunosuppressive Agents - pharmacokinetics ; Injections, Intravenous ; Male ; Medical sciences ; Pharmacology. Drug treatments ; Rats ; Rats, Wistar</subject><ispartof>European journal of drug metabolism and pharmacokinetics, 2004-04, Vol.29 (2), p.119-123</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c313t-7272219c37b86432f538be9ed51b2342bdcfaafa6b38a8027e54007b8aa3e37b3</citedby><cites>FETCH-LOGICAL-c313t-7272219c37b86432f538be9ed51b2342bdcfaafa6b38a8027e54007b8aa3e37b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15802309$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15230340$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KALKAN, Sule</creatorcontrib><creatorcontrib>GUMUSTEKIN, Mukaddes</creatorcontrib><creatorcontrib>AYGOREN, Oguz</creatorcontrib><creatorcontrib>TUNCOK, Yesim</creatorcontrib><creatorcontrib>GELAL, Ayse</creatorcontrib><creatorcontrib>GUVEN, Hulya</creatorcontrib><title>The interaction of the diltiazem with oral and intravenous cyclosporine in rats</title><title>European journal of drug metabolism and pharmacokinetics</title><addtitle>Eur J Drug Metab Pharmacokinet</addtitle><description>This study investigated the effect of diltiazem on the bioavailability of oral and intravenous cyclosporine (CsA) in rats. While control rats received normal saline, experimental groups received 60 or 90 mg/kg diltiazem orally for 3 days. Each group divided into 2 equal groups that received a single oral dose or i.v. injection of CsA. Pharmacokinetic parameters were analyzed by nonparametric analysis of variance. Pretreatment with 60 or 90 mg/kg diltiazem decreased the area under the blood CsA concentration-time curve (AUC) of oral CsA compared to control group (54.5% and 65.5% for AUC(0-24), 57.6% and 62.2% for AUC(0-infinity), respectively, p<0.05). Mean CsA maximum concentration (Cmax) decreased from 0.4 +/- 0.1 microg/ml to 0.1 +/- 0.0 microg/mL in rats pretreated with 90 mg/kg diltiazem (p<0.05). The absolute bioavailability after oral administration (F(p.o.)) in the 60 or 90 mg/kg diltiazem groups were lower than the control group (9.6% and 8.5% versus 22.6%). Pretreatment with 90 mg/kg but not 60 mg/kg of diltiazem increased the AUC(0-infinity), elimination half-life (t1/2) of intravenous CsA (116.0%, 219.2%, respectively, p<0.05) and decreased the intravenous CsA clearence (CL(i.v.)) (62.9%, p<0.05). Diltiazem decreased the bioavailability of oral CsA, while it increased the bioavailability of intravenous CsA. One must consider this interaction when administering oral or intravenous CsA concomitantly with diltiazem.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Antihypertensive agents</subject><subject>Area Under Curve</subject><subject>Biological and medical sciences</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Cardiovascular system</subject><subject>Cyclosporine - pharmacokinetics</subject><subject>Diltiazem - pharmacology</subject><subject>Drug Interactions</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Wistar</subject><issn>0378-7966</issn><issn>2107-0180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkMFKw0AQhhdRbKm9-ACyFy9CdHYnm90ctVgVCr3Uc5hsNnQlTcpuqtSnN6WFOpeB4ZufmY-xWwGPAkA_vcwBRQ7KZBdsLAXoBISBSzYG1CbReZaN2DTGLxgKTa5Uds1GQkkETGHMlqu1477tXSDb-67lXc37YVT5pvf06zb8x_dr3gVqOLXVAQ307dpuF7nd26aL2y749pDBA_Xxhl3V1EQ3PfUJ-5y_rmbvyWL59jF7XiQWBfaJllpKkVvUpclSlLVCU7rcVUqUElNZVrYmqikr0ZABqZ1Kh29LQ4RuWMIJezjm2tDFGFxdbIPfUNgXAoqDmOIsZoDvjvB2V25cdUZPGgbg_gRQtNTUgVrr4z9uOAEhxz8HkGoh</recordid><startdate>20040401</startdate><enddate>20040401</enddate><creator>KALKAN, Sule</creator><creator>GUMUSTEKIN, Mukaddes</creator><creator>AYGOREN, Oguz</creator><creator>TUNCOK, Yesim</creator><creator>GELAL, Ayse</creator><creator>GUVEN, Hulya</creator><general>Médecine et hygiène</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></search><sort><creationdate>20040401</creationdate><title>The interaction of the diltiazem with oral and intravenous cyclosporine in rats</title><author>KALKAN, Sule ; GUMUSTEKIN, Mukaddes ; AYGOREN, Oguz ; TUNCOK, Yesim ; GELAL, Ayse ; GUVEN, Hulya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c313t-7272219c37b86432f538be9ed51b2342bdcfaafa6b38a8027e54007b8aa3e37b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Antihypertensive agents</topic><topic>Area Under Curve</topic><topic>Biological and medical sciences</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Cardiovascular system</topic><topic>Cyclosporine - pharmacokinetics</topic><topic>Diltiazem - pharmacology</topic><topic>Drug Interactions</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Wistar</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KALKAN, Sule</creatorcontrib><creatorcontrib>GUMUSTEKIN, Mukaddes</creatorcontrib><creatorcontrib>AYGOREN, Oguz</creatorcontrib><creatorcontrib>TUNCOK, Yesim</creatorcontrib><creatorcontrib>GELAL, Ayse</creatorcontrib><creatorcontrib>GUVEN, Hulya</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><jtitle>European journal of drug metabolism and pharmacokinetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KALKAN, Sule</au><au>GUMUSTEKIN, Mukaddes</au><au>AYGOREN, Oguz</au><au>TUNCOK, Yesim</au><au>GELAL, Ayse</au><au>GUVEN, Hulya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The interaction of the diltiazem with oral and intravenous cyclosporine in rats</atitle><jtitle>European journal of drug metabolism and pharmacokinetics</jtitle><addtitle>Eur J Drug Metab Pharmacokinet</addtitle><date>2004-04-01</date><risdate>2004</risdate><volume>29</volume><issue>2</issue><spage>119</spage><epage>123</epage><pages>119-123</pages><issn>0378-7966</issn><eissn>2107-0180</eissn><abstract>This study investigated the effect of diltiazem on the bioavailability of oral and intravenous cyclosporine (CsA) in rats. While control rats received normal saline, experimental groups received 60 or 90 mg/kg diltiazem orally for 3 days. Each group divided into 2 equal groups that received a single oral dose or i.v. injection of CsA. Pharmacokinetic parameters were analyzed by nonparametric analysis of variance. Pretreatment with 60 or 90 mg/kg diltiazem decreased the area under the blood CsA concentration-time curve (AUC) of oral CsA compared to control group (54.5% and 65.5% for AUC(0-24), 57.6% and 62.2% for AUC(0-infinity), respectively, p<0.05). Mean CsA maximum concentration (Cmax) decreased from 0.4 +/- 0.1 microg/ml to 0.1 +/- 0.0 microg/mL in rats pretreated with 90 mg/kg diltiazem (p<0.05). The absolute bioavailability after oral administration (F(p.o.)) in the 60 or 90 mg/kg diltiazem groups were lower than the control group (9.6% and 8.5% versus 22.6%). Pretreatment with 90 mg/kg but not 60 mg/kg of diltiazem increased the AUC(0-infinity), elimination half-life (t1/2) of intravenous CsA (116.0%, 219.2%, respectively, p<0.05) and decreased the intravenous CsA clearence (CL(i.v.)) (62.9%, p<0.05). Diltiazem decreased the bioavailability of oral CsA, while it increased the bioavailability of intravenous CsA. One must consider this interaction when administering oral or intravenous CsA concomitantly with diltiazem.</abstract><cop>Genève</cop><pub>Médecine et hygiène</pub><pmid>15230340</pmid><doi>10.1007/BF03190586</doi><tpages>5</tpages></addata></record> |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Administration, Oral Animals Antihypertensive agents Area Under Curve Biological and medical sciences Calcium Channel Blockers - pharmacology Cardiovascular system Cyclosporine - pharmacokinetics Diltiazem - pharmacology Drug Interactions Immunosuppressive Agents - pharmacokinetics Injections, Intravenous Male Medical sciences Pharmacology. Drug treatments Rats Rats, Wistar |
| title | The interaction of the diltiazem with oral and intravenous cyclosporine in rats |
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