Age-related changes in the pharmacodynamics of verapamil
Age-related differences in the pharmacodynamics of numerous drugs are well documented. In this study, changes in the pharmacodynamics of verapamil were examined in anesthetized and unanesthetized puppies (6 weeks old) and adult dogs. Unanesthetized puppies and adult dogs were given verapamil (0.5 mg...
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| Veröffentlicht in: | The American heart journal 1985-11, Vol.110 (5), p.981-985 |
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| container_title | The American heart journal |
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| creator | Arnold, T.H. Vallner, J.J. Tackett, R.L. |
| description | Age-related differences in the pharmacodynamics of numerous drugs are well documented. In this study, changes in the pharmacodynamics of verapamil were examined in anesthetized and unanesthetized puppies (6 weeks old) and adult dogs. Unanesthetized puppies and adult dogs were given verapamil (0.5 mg/kg intravenously and 2.5 mg/kg orally), and anesthetized dogs received only intravenous infusions. Plasma samples and ECG tracings were taken over a 4- to 7-hour period. Plasma verapamil was determined by high-pressure liquid chromatography with spectrofluorometric detection. Puppies exhibited a shorter
t
1
2
than adults after intravenous administration (62.3 ± 10.8 minutes compared to 87.3 ± 7.8 minutes). Puppies had a greater area under concentration (AUC) after oral dosing than adults, indicating a greater amount of the dose reaching the systemic circulation. The PR interval was significantly prolonged in adults but not in puppies, even though the blood levels in the puppies were greater than those in the adults. Therefore, even though there is little variation in the pharmacokinetic parameters between adult dogs and puppies, there is a marked reduction in the sensitivity of the puppies to the ECG effects of verapamil. |
| doi_str_mv | 10.1016/0002-8703(85)90196-6 |
| format | Article |
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t
1
2
than adults after intravenous administration (62.3 ± 10.8 minutes compared to 87.3 ± 7.8 minutes). Puppies had a greater area under concentration (AUC) after oral dosing than adults, indicating a greater amount of the dose reaching the systemic circulation. The PR interval was significantly prolonged in adults but not in puppies, even though the blood levels in the puppies were greater than those in the adults. Therefore, even though there is little variation in the pharmacokinetic parameters between adult dogs and puppies, there is a marked reduction in the sensitivity of the puppies to the ECG effects of verapamil.</description><identifier>ISSN: 0002-8703</identifier><identifier>EISSN: 1097-6744</identifier><identifier>DOI: 10.1016/0002-8703(85)90196-6</identifier><identifier>PMID: 4061274</identifier><identifier>CODEN: AHJOA2</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Administration, Oral ; Aging ; Anesthesia ; Animals ; Antiarythmic agents ; Biological and medical sciences ; Blood Pressure - drug effects ; Cardiovascular system ; Dogs ; Electrocardiography ; Electrophysiology ; Heart Rate - drug effects ; Injections, Intravenous ; Kinetics ; Medical sciences ; Pharmacology. Drug treatments ; Time Factors ; Verapamil - administration & dosage ; Verapamil - metabolism</subject><ispartof>The American heart journal, 1985-11, Vol.110 (5), p.981-985</ispartof><rights>1985</rights><rights>1986 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-cb91f2f3005534b1ed9e9c8de9d7f0c97801cca7f917eae507aab534bea54e723</citedby><cites>FETCH-LOGICAL-c386t-cb91f2f3005534b1ed9e9c8de9d7f0c97801cca7f917eae507aab534bea54e723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0002-8703(85)90196-6$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8426428$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/4061274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arnold, T.H.</creatorcontrib><creatorcontrib>Vallner, J.J.</creatorcontrib><creatorcontrib>Tackett, R.L.</creatorcontrib><title>Age-related changes in the pharmacodynamics of verapamil</title><title>The American heart journal</title><addtitle>Am Heart J</addtitle><description>Age-related differences in the pharmacodynamics of numerous drugs are well documented. In this study, changes in the pharmacodynamics of verapamil were examined in anesthetized and unanesthetized puppies (6 weeks old) and adult dogs. Unanesthetized puppies and adult dogs were given verapamil (0.5 mg/kg intravenously and 2.5 mg/kg orally), and anesthetized dogs received only intravenous infusions. Plasma samples and ECG tracings were taken over a 4- to 7-hour period. Plasma verapamil was determined by high-pressure liquid chromatography with spectrofluorometric detection. Puppies exhibited a shorter
t
1
2
than adults after intravenous administration (62.3 ± 10.8 minutes compared to 87.3 ± 7.8 minutes). Puppies had a greater area under concentration (AUC) after oral dosing than adults, indicating a greater amount of the dose reaching the systemic circulation. The PR interval was significantly prolonged in adults but not in puppies, even though the blood levels in the puppies were greater than those in the adults. Therefore, even though there is little variation in the pharmacokinetic parameters between adult dogs and puppies, there is a marked reduction in the sensitivity of the puppies to the ECG effects of verapamil.</description><subject>Administration, Oral</subject><subject>Aging</subject><subject>Anesthesia</subject><subject>Animals</subject><subject>Antiarythmic agents</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Cardiovascular system</subject><subject>Dogs</subject><subject>Electrocardiography</subject><subject>Electrophysiology</subject><subject>Heart Rate - drug effects</subject><subject>Injections, Intravenous</subject><subject>Kinetics</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Time Factors</subject><subject>Verapamil - administration & dosage</subject><subject>Verapamil - metabolism</subject><issn>0002-8703</issn><issn>1097-6744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1Lw0AQhhdRaq3-A4UcRPQQ3U02-3ERSvELCl70vEw2E7uSj7qbFvrvTWzo0dPwMs87DA8hl4zeM8rEA6U0iZWk6a3K7jRlWsTiiEwZ1TIWkvNjMj0gp-QshO8-ikSJCZlwKlgi-ZSo-RfGHivosIjsCpovDJFrom6F0XoFvgbbFrsGamdD1JbRFj2s-1Sdk5MSqoAX45yRz-enj8VrvHx_eVvMl7FNlehim2tWJmVKaZalPGdYaNRWFagLWVKrpaLMWpClZhIBMyoB8oFEyDjKJJ2Rm_3dtW9_Nhg6U7tgsaqgwXYTjBS8L2WsB_ketL4NwWNp1t7V4HeGUTMIM4MNM9gwKjN_wozoa1fj_U1eY3EojYb6_fW4h2ChKj001oUDpngieKJ67HGPYe9i69CbYB02Fgvn0XamaN3_f_wCLgeGQg</recordid><startdate>198511</startdate><enddate>198511</enddate><creator>Arnold, T.H.</creator><creator>Vallner, J.J.</creator><creator>Tackett, R.L.</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>198511</creationdate><title>Age-related changes in the pharmacodynamics of verapamil</title><author>Arnold, T.H. ; Vallner, J.J. ; Tackett, R.L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-cb91f2f3005534b1ed9e9c8de9d7f0c97801cca7f917eae507aab534bea54e723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Administration, Oral</topic><topic>Aging</topic><topic>Anesthesia</topic><topic>Animals</topic><topic>Antiarythmic agents</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Cardiovascular system</topic><topic>Dogs</topic><topic>Electrocardiography</topic><topic>Electrophysiology</topic><topic>Heart Rate - drug effects</topic><topic>Injections, Intravenous</topic><topic>Kinetics</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Time Factors</topic><topic>Verapamil - administration & dosage</topic><topic>Verapamil - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arnold, T.H.</creatorcontrib><creatorcontrib>Vallner, J.J.</creatorcontrib><creatorcontrib>Tackett, R.L.</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>The American heart journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arnold, T.H.</au><au>Vallner, J.J.</au><au>Tackett, R.L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Age-related changes in the pharmacodynamics of verapamil</atitle><jtitle>The American heart journal</jtitle><addtitle>Am Heart J</addtitle><date>1985-11</date><risdate>1985</risdate><volume>110</volume><issue>5</issue><spage>981</spage><epage>985</epage><pages>981-985</pages><issn>0002-8703</issn><eissn>1097-6744</eissn><coden>AHJOA2</coden><abstract>Age-related differences in the pharmacodynamics of numerous drugs are well documented. In this study, changes in the pharmacodynamics of verapamil were examined in anesthetized and unanesthetized puppies (6 weeks old) and adult dogs. Unanesthetized puppies and adult dogs were given verapamil (0.5 mg/kg intravenously and 2.5 mg/kg orally), and anesthetized dogs received only intravenous infusions. Plasma samples and ECG tracings were taken over a 4- to 7-hour period. Plasma verapamil was determined by high-pressure liquid chromatography with spectrofluorometric detection. Puppies exhibited a shorter
t
1
2
than adults after intravenous administration (62.3 ± 10.8 minutes compared to 87.3 ± 7.8 minutes). Puppies had a greater area under concentration (AUC) after oral dosing than adults, indicating a greater amount of the dose reaching the systemic circulation. The PR interval was significantly prolonged in adults but not in puppies, even though the blood levels in the puppies were greater than those in the adults. Therefore, even though there is little variation in the pharmacokinetic parameters between adult dogs and puppies, there is a marked reduction in the sensitivity of the puppies to the ECG effects of verapamil.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>4061274</pmid><doi>10.1016/0002-8703(85)90196-6</doi><tpages>5</tpages></addata></record> |
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| ispartof | The American heart journal, 1985-11, Vol.110 (5), p.981-985 |
| issn | 0002-8703 1097-6744 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Administration, Oral Aging Anesthesia Animals Antiarythmic agents Biological and medical sciences Blood Pressure - drug effects Cardiovascular system Dogs Electrocardiography Electrophysiology Heart Rate - drug effects Injections, Intravenous Kinetics Medical sciences Pharmacology. Drug treatments Time Factors Verapamil - administration & dosage Verapamil - metabolism |
| title | Age-related changes in the pharmacodynamics of verapamil |
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