Pre-systemic metabolism of viprostol in the monkey following oral and topical administration
1. 14C-Viprostol, (I), a synthetic PGE2 analogue, was administered to 6 monkeys, orally, topically and intravenously in a three way crossover study. Total radioactivity and the pharmacologically active acid formed by rapid hydolysis of viprostol in vivo, (II), were measured in plasma to determine ab...
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| Veröffentlicht in: | Xenobiotica 1988, Vol.18 (7), p.797-802 |
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| container_title | Xenobiotica |
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| creator | Nicolau, G. Tonelli, A. P. Cosulich, D. B. Perkinson, N. A. Dicioccio, A. T. McWilliams, W. E. Yacobi, A. |
| description | 1. 14C-Viprostol, (I), a synthetic PGE2 analogue, was administered to 6 monkeys, orally, topically and intravenously in a three way crossover study. Total radioactivity and the pharmacologically active acid formed by rapid hydolysis of viprostol in vivo, (II), were measured in plasma to determine absorption and absolute bioavailability.
2. After oral dosing approx. 31% of drug-related radioactivity was absorbed. Systemic bioavailability of unchanged active acid was only 7 3%. This indicates significant first-pass metabolism after oral administration, since only 23% of the absorbed radioactivity was available as 'unchanged' active drug (II).
3. After topical dosing, transdermal absorption of total radioactivity by 48 h averaged only 5% of dose. Absolute bioavailability of II averaged 3 8% of dose. This indicates that after transdermal absorption 74% of the absorbed radioactivity was available systemically as the active acid II, with the remainder being subject to pre-systemic metabolism. |
| doi_str_mv | 10.3109/00498258809041718 |
| format | Article |
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2. After oral dosing approx. 31% of drug-related radioactivity was absorbed. Systemic bioavailability of unchanged active acid was only 7 3%. This indicates significant first-pass metabolism after oral administration, since only 23% of the absorbed radioactivity was available as 'unchanged' active drug (II).
3. After topical dosing, transdermal absorption of total radioactivity by 48 h averaged only 5% of dose. Absolute bioavailability of II averaged 3 8% of dose. This indicates that after transdermal absorption 74% of the absorbed radioactivity was available systemically as the active acid II, with the remainder being subject to pre-systemic metabolism.</description><identifier>ISSN: 0049-8254</identifier><identifier>EISSN: 1366-5928</identifier><identifier>DOI: 10.3109/00498258809041718</identifier><identifier>PMID: 3176518</identifier><identifier>CODEN: XENOBH</identifier><language>eng</language><publisher>London: Informa UK Ltd</publisher><subject>Absorption ; Administration, Oral ; Administration, Topical ; Animals ; Antihypertensive Agents ; Biological and medical sciences ; Biological Availability ; Dinoprostone - administration & dosage ; Dinoprostone - analogs & derivatives ; Dinoprostone - pharmacokinetics ; Injections, Intravenous ; Macaca fascicularis ; Male ; Medical sciences ; Miscellaneous ; Pharmacology. Drug treatments</subject><ispartof>Xenobiotica, 1988, Vol.18 (7), p.797-802</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-4719d7608f2b17a2830abe2ef4efff1bd19a52aa8b297091485deaa883f000ae3</citedby><cites>FETCH-LOGICAL-c430t-4719d7608f2b17a2830abe2ef4efff1bd19a52aa8b297091485deaa883f000ae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.3109/00498258809041718$$EPDF$$P50$$Ginformahealthcare$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.3109/00498258809041718$$EHTML$$P50$$Ginformahealthcare$$H</linktohtml><link.rule.ids>314,780,784,4024,27923,27924,27925,59647,59753,60436,60542,61221,61256,61402,61437</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7161213$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3176518$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nicolau, G.</creatorcontrib><creatorcontrib>Tonelli, A. P.</creatorcontrib><creatorcontrib>Cosulich, D. B.</creatorcontrib><creatorcontrib>Perkinson, N. A.</creatorcontrib><creatorcontrib>Dicioccio, A. T.</creatorcontrib><creatorcontrib>McWilliams, W. E.</creatorcontrib><creatorcontrib>Yacobi, A.</creatorcontrib><title>Pre-systemic metabolism of viprostol in the monkey following oral and topical administration</title><title>Xenobiotica</title><addtitle>Xenobiotica</addtitle><description>1. 14C-Viprostol, (I), a synthetic PGE2 analogue, was administered to 6 monkeys, orally, topically and intravenously in a three way crossover study. Total radioactivity and the pharmacologically active acid formed by rapid hydolysis of viprostol in vivo, (II), were measured in plasma to determine absorption and absolute bioavailability.
2. After oral dosing approx. 31% of drug-related radioactivity was absorbed. Systemic bioavailability of unchanged active acid was only 7 3%. This indicates significant first-pass metabolism after oral administration, since only 23% of the absorbed radioactivity was available as 'unchanged' active drug (II).
3. After topical dosing, transdermal absorption of total radioactivity by 48 h averaged only 5% of dose. Absolute bioavailability of II averaged 3 8% of dose. This indicates that after transdermal absorption 74% of the absorbed radioactivity was available systemically as the active acid II, with the remainder being subject to pre-systemic metabolism.</description><subject>Absorption</subject><subject>Administration, Oral</subject><subject>Administration, Topical</subject><subject>Animals</subject><subject>Antihypertensive Agents</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Dinoprostone - administration & dosage</subject><subject>Dinoprostone - analogs & derivatives</subject><subject>Dinoprostone - pharmacokinetics</subject><subject>Injections, Intravenous</subject><subject>Macaca fascicularis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Pharmacology. 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E. ; Yacobi, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-4719d7608f2b17a2830abe2ef4efff1bd19a52aa8b297091485deaa883f000ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>Absorption</topic><topic>Administration, Oral</topic><topic>Administration, Topical</topic><topic>Animals</topic><topic>Antihypertensive Agents</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Dinoprostone - administration & dosage</topic><topic>Dinoprostone - analogs & derivatives</topic><topic>Dinoprostone - pharmacokinetics</topic><topic>Injections, Intravenous</topic><topic>Macaca fascicularis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nicolau, G.</creatorcontrib><creatorcontrib>Tonelli, A. P.</creatorcontrib><creatorcontrib>Cosulich, D. B.</creatorcontrib><creatorcontrib>Perkinson, N. A.</creatorcontrib><creatorcontrib>Dicioccio, A. T.</creatorcontrib><creatorcontrib>McWilliams, W. E.</creatorcontrib><creatorcontrib>Yacobi, 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>Nicolau, G.</au><au>Tonelli, A. P.</au><au>Cosulich, D. B.</au><au>Perkinson, N. A.</au><au>Dicioccio, A. T.</au><au>McWilliams, W. E.</au><au>Yacobi, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pre-systemic metabolism of viprostol in the monkey following oral and topical administration</atitle><jtitle>Xenobiotica</jtitle><addtitle>Xenobiotica</addtitle><date>1988</date><risdate>1988</risdate><volume>18</volume><issue>7</issue><spage>797</spage><epage>802</epage><pages>797-802</pages><issn>0049-8254</issn><eissn>1366-5928</eissn><coden>XENOBH</coden><abstract>1. 14C-Viprostol, (I), a synthetic PGE2 analogue, was administered to 6 monkeys, orally, topically and intravenously in a three way crossover study. Total radioactivity and the pharmacologically active acid formed by rapid hydolysis of viprostol in vivo, (II), were measured in plasma to determine absorption and absolute bioavailability.
2. After oral dosing approx. 31% of drug-related radioactivity was absorbed. Systemic bioavailability of unchanged active acid was only 7 3%. This indicates significant first-pass metabolism after oral administration, since only 23% of the absorbed radioactivity was available as 'unchanged' active drug (II).
3. After topical dosing, transdermal absorption of total radioactivity by 48 h averaged only 5% of dose. Absolute bioavailability of II averaged 3 8% of dose. This indicates that after transdermal absorption 74% of the absorbed radioactivity was available systemically as the active acid II, with the remainder being subject to pre-systemic metabolism.</abstract><cop>London</cop><pub>Informa UK Ltd</pub><pmid>3176518</pmid><doi>10.3109/00498258809041718</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Xenobiotica, 1988, Vol.18 (7), p.797-802 |
| issn | 0049-8254 1366-5928 |
| language | eng |
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| source | MEDLINE; Taylor & Francis:Master (3349 titles); Taylor & Francis Medical Library - CRKN |
| subjects | Absorption Administration, Oral Administration, Topical Animals Antihypertensive Agents Biological and medical sciences Biological Availability Dinoprostone - administration & dosage Dinoprostone - analogs & derivatives Dinoprostone - pharmacokinetics Injections, Intravenous Macaca fascicularis Male Medical sciences Miscellaneous Pharmacology. Drug treatments |
| title | Pre-systemic metabolism of viprostol in the monkey following oral and topical administration |
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