Metabolism of amlodipine in the rat and the dog: A species difference
1. Following oral and i.v. doses of 14C-amlodipine to rat and dog, 40-50% of the dose was excreted in the urine indicating that the oral dose was well absorbed. Urinary and faecal excretion in rat was essentially complete within 48 h but was prolonged during 168 h in dog. 2. Metabolite patterns were...
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| Veröffentlicht in: | Xenobiotica 1988, Vol.18 (2), p.169-182 |
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| creator | Beresford, A. P. Macrae, P. V. Stopher, D. A. |
| description | 1. Following oral and i.v. doses of 14C-amlodipine to rat and dog, 40-50% of the dose was excreted in the urine indicating that the oral dose was well absorbed. Urinary and faecal excretion in rat was essentially complete within 48 h but was prolonged during 168 h in dog.
2. Metabolite patterns were dissimilar for rat and dog for both urine and faeces. The majority (about 95%) of the urinary metabolites were identified for both species; unchanged drug accounted for 10% and 2% of the urinary radioactivity in rat and dog respectively.
3. In rat, the principal route of metabolism involved cleavage of the 5-methoxy-carbonyl group of both the parent dihydropyridine and its pyridine analogue. In contrast, metabolism in dog involved oxidative deamination of the 2-aminoethoxy-methyl side-chain.
4. Secondary metabolism in both rat and dog was similar to that of other calcium channel blockers of the dihydropyridine class, with oxidation to the pyridine form being followed by aliphatic hydroxylation in the 6-position or O-dealkylation in the 2-position and lactonization. |
| doi_str_mv | 10.3109/00498258809041653 |
| format | Article |
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2. Metabolite patterns were dissimilar for rat and dog for both urine and faeces. The majority (about 95%) of the urinary metabolites were identified for both species; unchanged drug accounted for 10% and 2% of the urinary radioactivity in rat and dog respectively.
3. In rat, the principal route of metabolism involved cleavage of the 5-methoxy-carbonyl group of both the parent dihydropyridine and its pyridine analogue. In contrast, metabolism in dog involved oxidative deamination of the 2-aminoethoxy-methyl side-chain.
4. Secondary metabolism in both rat and dog was similar to that of other calcium channel blockers of the dihydropyridine class, with oxidation to the pyridine form being followed by aliphatic hydroxylation in the 6-position or O-dealkylation in the 2-position and lactonization.</description><identifier>ISSN: 0049-8254</identifier><identifier>EISSN: 1366-5928</identifier><identifier>DOI: 10.3109/00498258809041653</identifier><identifier>PMID: 2967592</identifier><identifier>CODEN: XENOBH</identifier><language>eng</language><publisher>London: Informa UK Ltd</publisher><subject>Administration, Oral ; Amlodipine ; Animals ; Biological and medical sciences ; Cardiovascular system ; Chromatography, Thin Layer ; Dogs ; Feces - analysis ; Mass Spectrometry ; Medical sciences ; Nifedipine - analogs & derivatives ; Nifedipine - metabolism ; Pharmacology. Drug treatments ; Rats ; Species Specificity ; Vasodilator agents. Cerebral vasodilators</subject><ispartof>Xenobiotica, 1988, Vol.18 (2), p.169-182</ispartof><rights>1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 1988</rights><rights>1989 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-a3787c4db45759be658a89a53acddb8836c5d95f2f72d6eb61e79de39b33a7853</citedby><cites>FETCH-LOGICAL-c430t-a3787c4db45759be658a89a53acddb8836c5d95f2f72d6eb61e79de39b33a7853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.3109/00498258809041653$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.3109/00498258809041653$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,780,784,4024,27923,27924,27925,59647,59753,60436,60542,61221,61256,61402,61437</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=6987025$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2967592$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beresford, A. P.</creatorcontrib><creatorcontrib>Macrae, P. V.</creatorcontrib><creatorcontrib>Stopher, D. A.</creatorcontrib><title>Metabolism of amlodipine in the rat and the dog: A species difference</title><title>Xenobiotica</title><addtitle>Xenobiotica</addtitle><description>1. Following oral and i.v. doses of 14C-amlodipine to rat and dog, 40-50% of the dose was excreted in the urine indicating that the oral dose was well absorbed. Urinary and faecal excretion in rat was essentially complete within 48 h but was prolonged during 168 h in dog.
2. Metabolite patterns were dissimilar for rat and dog for both urine and faeces. The majority (about 95%) of the urinary metabolites were identified for both species; unchanged drug accounted for 10% and 2% of the urinary radioactivity in rat and dog respectively.
3. In rat, the principal route of metabolism involved cleavage of the 5-methoxy-carbonyl group of both the parent dihydropyridine and its pyridine analogue. In contrast, metabolism in dog involved oxidative deamination of the 2-aminoethoxy-methyl side-chain.
4. Secondary metabolism in both rat and dog was similar to that of other calcium channel blockers of the dihydropyridine class, with oxidation to the pyridine form being followed by aliphatic hydroxylation in the 6-position or O-dealkylation in the 2-position and lactonization.</description><subject>Administration, Oral</subject><subject>Amlodipine</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Chromatography, Thin Layer</subject><subject>Dogs</subject><subject>Feces - analysis</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Nifedipine - analogs & derivatives</subject><subject>Nifedipine - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Species Specificity</subject><subject>Vasodilator agents. Cerebral vasodilators</subject><issn>0049-8254</issn><issn>1366-5928</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9P3DAQxa2KChbaD9ADkg-ot7SOHTs2cEEIaCWqXtpzNLHHXSMnXuysEN--WXZBQkicZqT3e_PnEfKlZt9Ezcx3xhqjudSaGdbUSooPZFELpSppuN4ji41ezUBzQA5LuWOMqZrzfbLPjWpnZkGufuEEfYqhDDR5CkNMLqzCiDSMdFoizTBRGN1T79K_U3pBywptwEJd8B4zjhY_kY8eYsHPu3pE_l5f_bn8Ud3-vvl5eXFb2UawqQLR6tY2rm_kvL1HJTVoA1KAda7XWigrnZGe-5Y7hb2qsTUOhemFgFZLcUS-bueucrpfY5m6IRSLMcKIaV26dv6Vc9XMYL0FbU6lZPTdKocB8mNXs24TXfcmutlzvBu-7gd0L45dVrN-stOhWIg-w2hDecGU0S3jmxvPt1gYfcoDPKQcXTfBY0z52SPeu-LslX2JEKelhYzdXVrncY73nR_-A3JHmgQ</recordid><startdate>1988</startdate><enddate>1988</enddate><creator>Beresford, A. P.</creator><creator>Macrae, P. V.</creator><creator>Stopher, D. A.</creator><general>Informa UK Ltd</general><general>Taylor & Francis</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>1988</creationdate><title>Metabolism of amlodipine in the rat and the dog: A species difference</title><author>Beresford, A. P. ; Macrae, P. V. ; Stopher, D. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-a3787c4db45759be658a89a53acddb8836c5d95f2f72d6eb61e79de39b33a7853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>Administration, Oral</topic><topic>Amlodipine</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular system</topic><topic>Chromatography, Thin Layer</topic><topic>Dogs</topic><topic>Feces - analysis</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Nifedipine - analogs & derivatives</topic><topic>Nifedipine - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Species Specificity</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beresford, A. P.</creatorcontrib><creatorcontrib>Macrae, P. V.</creatorcontrib><creatorcontrib>Stopher, D. A.</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>Xenobiotica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beresford, A. P.</au><au>Macrae, P. V.</au><au>Stopher, D. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolism of amlodipine in the rat and the dog: A species difference</atitle><jtitle>Xenobiotica</jtitle><addtitle>Xenobiotica</addtitle><date>1988</date><risdate>1988</risdate><volume>18</volume><issue>2</issue><spage>169</spage><epage>182</epage><pages>169-182</pages><issn>0049-8254</issn><eissn>1366-5928</eissn><coden>XENOBH</coden><abstract>1. Following oral and i.v. doses of 14C-amlodipine to rat and dog, 40-50% of the dose was excreted in the urine indicating that the oral dose was well absorbed. Urinary and faecal excretion in rat was essentially complete within 48 h but was prolonged during 168 h in dog.
2. Metabolite patterns were dissimilar for rat and dog for both urine and faeces. The majority (about 95%) of the urinary metabolites were identified for both species; unchanged drug accounted for 10% and 2% of the urinary radioactivity in rat and dog respectively.
3. In rat, the principal route of metabolism involved cleavage of the 5-methoxy-carbonyl group of both the parent dihydropyridine and its pyridine analogue. In contrast, metabolism in dog involved oxidative deamination of the 2-aminoethoxy-methyl side-chain.
4. Secondary metabolism in both rat and dog was similar to that of other calcium channel blockers of the dihydropyridine class, with oxidation to the pyridine form being followed by aliphatic hydroxylation in the 6-position or O-dealkylation in the 2-position and lactonization.</abstract><cop>London</cop><pub>Informa UK Ltd</pub><pmid>2967592</pmid><doi>10.3109/00498258809041653</doi><tpages>14</tpages></addata></record> |
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| ispartof | Xenobiotica, 1988, Vol.18 (2), p.169-182 |
| issn | 0049-8254 1366-5928 |
| language | eng |
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| source | MEDLINE; Taylor & Francis Medical Library - CRKN; Taylor & Francis Journals Complete |
| subjects | Administration, Oral Amlodipine Animals Biological and medical sciences Cardiovascular system Chromatography, Thin Layer Dogs Feces - analysis Mass Spectrometry Medical sciences Nifedipine - analogs & derivatives Nifedipine - metabolism Pharmacology. Drug treatments Rats Species Specificity Vasodilator agents. Cerebral vasodilators |
| title | Metabolism of amlodipine in the rat and the dog: A species difference |
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