Long-Term Systemic Exposure of Orlistat, a Lipase Inhibitor, and Its Metabolites in Obese Patients
Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract; its systemic exposure is not required for its efficacy. However, knowledge of the extent of its systemic exposure is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening in ob...
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| Veröffentlicht in: | Journal of clinical pharmacology 1999-01, Vol.39 (1), p.41-46 |
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| creator | Zhi, Jianguo Mulligan, Thomas E. Hauptman, Jonathan B. |
| description | Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract; its systemic exposure is not required for its efficacy. However, knowledge of the extent of its systemic exposure is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening in obese patients was carried out by monitoring plasma concentrations of unchanged orlistat and its metabolites in five key double‐blind, placebo‐controlled phase II/III studies. Results of these studies involving the monitoring of plasma samples indicate that detection of intact orlistat in plasma was sporadic, and measurable concentrations were low ( |
| doi_str_mv | 10.1177/00912709922007543 |
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However, knowledge of the extent of its systemic exposure is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening in obese patients was carried out by monitoring plasma concentrations of unchanged orlistat and its metabolites in five key double‐blind, placebo‐controlled phase II/III studies. Results of these studies involving the monitoring of plasma samples indicate that detection of intact orlistat in plasma was sporadic, and measurable concentrations were low (<10 ng/mL or 0.02 μM) without evidence of accumulation, which is consistent with minimal absorption. It is concluded that systemic exposure of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1177/00912709922007543</identifier><identifier>PMID: 9987699</identifier><identifier>CODEN: JCPCBR</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Biological and medical sciences ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Administration Schedule ; Enzyme Inhibitors - adverse effects ; Enzyme Inhibitors - metabolism ; Enzyme Inhibitors - pharmacokinetics ; Gastrointestinal Diseases - chemically induced ; General and cellular metabolism. Vitamins ; Humans ; Lactones - adverse effects ; Lactones - metabolism ; Lactones - pharmacokinetics ; Lipase - antagonists & inhibitors ; Medical sciences ; Obesity - drug therapy ; Orlistat ; Pharmacology. Drug treatments ; Time Factors ; Treatment Outcome</subject><ispartof>Journal of clinical pharmacology, 1999-01, Vol.39 (1), p.41-46</ispartof><rights>1999 American College of Clinical Pharmacology</rights><rights>1999 SAGE Publications</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5214-98a031220e68fcf611188171b028eb079c326d92dbfdb074aebbe0495418d20e3</citedby><cites>FETCH-LOGICAL-c5214-98a031220e68fcf611188171b028eb079c326d92dbfdb074aebbe0495418d20e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1177%2F00912709922007543$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1177%2F00912709922007543$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,4010,27900,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1674208$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9987699$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhi, Jianguo</creatorcontrib><creatorcontrib>Mulligan, Thomas E.</creatorcontrib><creatorcontrib>Hauptman, Jonathan B.</creatorcontrib><title>Long-Term Systemic Exposure of Orlistat, a Lipase Inhibitor, and Its Metabolites in Obese Patients</title><title>Journal of clinical pharmacology</title><addtitle>J Clin Pharmacol</addtitle><description>Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract; its systemic exposure is not required for its efficacy. However, knowledge of the extent of its systemic exposure is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening in obese patients was carried out by monitoring plasma concentrations of unchanged orlistat and its metabolites in five key double‐blind, placebo‐controlled phase II/III studies. Results of these studies involving the monitoring of plasma samples indicate that detection of intact orlistat in plasma was sporadic, and measurable concentrations were low (<10 ng/mL or 0.02 μM) without evidence of accumulation, which is consistent with minimal absorption. It is concluded that systemic exposure of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition.</description><subject>Biological and medical sciences</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Drug Administration Schedule</subject><subject>Enzyme Inhibitors - adverse effects</subject><subject>Enzyme Inhibitors - metabolism</subject><subject>Enzyme Inhibitors - pharmacokinetics</subject><subject>Gastrointestinal Diseases - chemically induced</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Humans</subject><subject>Lactones - adverse effects</subject><subject>Lactones - metabolism</subject><subject>Lactones - pharmacokinetics</subject><subject>Lipase - antagonists & inhibitors</subject><subject>Medical sciences</subject><subject>Obesity - drug therapy</subject><subject>Orlistat</subject><subject>Pharmacology. Drug treatments</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFvEzEQhS0EKqHwAzgg-cCxW8Zer70-QtQ0QYFUUOjRsndnielmN7Idtfn3uE1UDhw4WTPvfWP7DSFvGZwzptQHAM24Aq05B1CVKJ-RCasqXggJ4jmZPOhFNsBL8irG3wBMioqdkBOtayW1nhC3HIdfxTWGDf2-jwk3vqEX99sx7gLSsaOr0PuYbDqjli791kaki2HtnU9jyL2hpYsU6RdM1o29TxipH-jKYfZd2eRxSPE1edHZPuKb43lKfswurqfzYrm6XEw_Loum4kwUurZQsvwRlHXXdJIxVtdMMQe8RgdKNyWXreat69pcCovOIQhdCVa3mSpPCTvMbcIYY8DObIPf2LA3DMxDXOafuDLz7sBsd26D7RNxzCfr74-6jY3tu2CHxse_g6USHOpsEwfb3dgnDPG2391hMGu0fVrnawFEXkLBtNbAclU8tjImj5jvcf__55rP06s51zyDxQHMu8H7J9CGWyNVqSpz8_XSzG7mP6fy28x8Kv8AVzKe2g</recordid><startdate>199901</startdate><enddate>199901</enddate><creator>Zhi, Jianguo</creator><creator>Mulligan, Thomas E.</creator><creator>Hauptman, Jonathan B.</creator><general>Blackwell Publishing Ltd</general><general>SAGE Publications</general><general>Sage Science</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></search><sort><creationdate>199901</creationdate><title>Long-Term Systemic Exposure of Orlistat, a Lipase Inhibitor, and Its Metabolites in Obese Patients</title><author>Zhi, Jianguo ; Mulligan, Thomas E. ; Hauptman, Jonathan B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5214-98a031220e68fcf611188171b028eb079c326d92dbfdb074aebbe0495418d20e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Biological and medical sciences</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Drug Administration Schedule</topic><topic>Enzyme Inhibitors - adverse effects</topic><topic>Enzyme Inhibitors - metabolism</topic><topic>Enzyme Inhibitors - pharmacokinetics</topic><topic>Gastrointestinal Diseases - chemically induced</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Humans</topic><topic>Lactones - adverse effects</topic><topic>Lactones - metabolism</topic><topic>Lactones - pharmacokinetics</topic><topic>Lipase - antagonists & inhibitors</topic><topic>Medical sciences</topic><topic>Obesity - drug therapy</topic><topic>Orlistat</topic><topic>Pharmacology. Drug treatments</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhi, Jianguo</creatorcontrib><creatorcontrib>Mulligan, Thomas E.</creatorcontrib><creatorcontrib>Hauptman, Jonathan B.</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><jtitle>Journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhi, Jianguo</au><au>Mulligan, Thomas E.</au><au>Hauptman, Jonathan B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-Term Systemic Exposure of Orlistat, a Lipase Inhibitor, and Its Metabolites in Obese Patients</atitle><jtitle>Journal of clinical pharmacology</jtitle><addtitle>J Clin Pharmacol</addtitle><date>1999-01</date><risdate>1999</risdate><volume>39</volume><issue>1</issue><spage>41</spage><epage>46</epage><pages>41-46</pages><issn>0091-2700</issn><eissn>1552-4604</eissn><coden>JCPCBR</coden><abstract>Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract; its systemic exposure is not required for its efficacy. However, knowledge of the extent of its systemic exposure is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening in obese patients was carried out by monitoring plasma concentrations of unchanged orlistat and its metabolites in five key double‐blind, placebo‐controlled phase II/III studies. Results of these studies involving the monitoring of plasma samples indicate that detection of intact orlistat in plasma was sporadic, and measurable concentrations were low (<10 ng/mL or 0.02 μM) without evidence of accumulation, which is consistent with minimal absorption. It is concluded that systemic exposure of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>9987699</pmid><doi>10.1177/00912709922007543</doi><tpages>6</tpages></addata></record> |
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| identifier | ISSN: 0091-2700 |
| ispartof | Journal of clinical pharmacology, 1999-01, Vol.39 (1), p.41-46 |
| issn | 0091-2700 1552-4604 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Biological and medical sciences Dose-Response Relationship, Drug Double-Blind Method Drug Administration Schedule Enzyme Inhibitors - adverse effects Enzyme Inhibitors - metabolism Enzyme Inhibitors - pharmacokinetics Gastrointestinal Diseases - chemically induced General and cellular metabolism. Vitamins Humans Lactones - adverse effects Lactones - metabolism Lactones - pharmacokinetics Lipase - antagonists & inhibitors Medical sciences Obesity - drug therapy Orlistat Pharmacology. Drug treatments Time Factors Treatment Outcome |
| title | Long-Term Systemic Exposure of Orlistat, a Lipase Inhibitor, and Its Metabolites in Obese Patients |
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