Pharmacokinetics of Zileuton and Its Metabolites in Patients with Renal Impairment
The pharmacokinetics of zileuton and its conjugated metabolites were evaluated in patients with chronic renal impairment. Five healthy volunteers (creatinine clearance >90 mL/min), five patients with renal failure requiring hemodialysis, six with mild (creatinine clearance, 60–90 mL/min), eight w...
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| Veröffentlicht in: | Journal of clinical pharmacology 1997-05, Vol.37 (5), p.395-404 |
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| container_title | Journal of clinical pharmacology |
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| creator | Awni, Walid M. Wong, Shekman Chu, Sou-yie Patterson, Karen Hansen, Robert Machinist, Joseph M. Drajesk, Jeff Keane, William F. Halstenson, Charles E. |
| description | The pharmacokinetics of zileuton and its conjugated metabolites were evaluated in patients with chronic renal impairment. Five healthy volunteers (creatinine clearance >90 mL/min), five patients with renal failure requiring hemodialysis, six with mild (creatinine clearance, 60–90 mL/min), eight with moderate (creatinine clearance, 30–59 mL/min), and six with severe (creatinine clearance |
| doi_str_mv | 10.1002/j.1552-4604.1997.tb04317.x |
| format | Article |
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Five healthy volunteers (creatinine clearance >90 mL/min), five patients with renal failure requiring hemodialysis, six with mild (creatinine clearance, 60–90 mL/min), eight with moderate (creatinine clearance, 30–59 mL/min), and six with severe (creatinine clearance <30 mL/min) renal impairment participated in the study. Zileuton was well tolerated by all participants including those with severe renal impairment and those receiving hemodialysis. The pharmacokinetics of zileuton were similar in healthy volunteers; in patients with mild, moderate and severe renal impairment; and in patients with renal failure requiring hemodialysis. The mean metabolite/parent‐area ratios for the pharmacologically inactive zileuton glucuronides progressively increased with the decline in renal function. A very small percentage of the administered zileuton dose (<0.5%) was removed by hemodialysis. Therefore, adjustment in the dose regimen of zileuton does not appear to be necessary for patients with various degrees of renal impairment and patients with renal failure requiring hemodialysis.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1002/j.1552-4604.1997.tb04317.x</identifier><identifier>PMID: 9156372</identifier><identifier>CODEN: JCPCBR</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Female ; Humans ; Hydroxyurea - administration & dosage ; Hydroxyurea - analogs & derivatives ; Hydroxyurea - pharmacokinetics ; Kidney Diseases - metabolism ; Kidney Diseases - physiopathology ; Kidney Failure, Chronic - metabolism ; Kidney Failure, Chronic - physiopathology ; Kidney Failure, Chronic - therapy ; Kidney Function Tests ; Lipoxygenase Inhibitors - administration & dosage ; Lipoxygenase Inhibitors - pharmacokinetics ; Male ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Renal Dialysis ; Respiratory system</subject><ispartof>Journal of clinical pharmacology, 1997-05, Vol.37 (5), p.395-404</ispartof><rights>1997 American College of Clinical Pharmacology</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4387-bb30d7bf05590dbea50c3693f56b7abad81993ce12c75e6b26d18ad03ba8be223</citedby><cites>FETCH-LOGICAL-c4387-bb30d7bf05590dbea50c3693f56b7abad81993ce12c75e6b26d18ad03ba8be223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fj.1552-4604.1997.tb04317.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fj.1552-4604.1997.tb04317.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2680468$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9156372$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Awni, Walid M.</creatorcontrib><creatorcontrib>Wong, Shekman</creatorcontrib><creatorcontrib>Chu, Sou-yie</creatorcontrib><creatorcontrib>Patterson, Karen</creatorcontrib><creatorcontrib>Hansen, Robert</creatorcontrib><creatorcontrib>Machinist, Joseph M.</creatorcontrib><creatorcontrib>Drajesk, Jeff</creatorcontrib><creatorcontrib>Keane, William F.</creatorcontrib><creatorcontrib>Halstenson, Charles E.</creatorcontrib><title>Pharmacokinetics of Zileuton and Its Metabolites in Patients with Renal Impairment</title><title>Journal of clinical pharmacology</title><addtitle>J Clin Pharmacol</addtitle><description>The pharmacokinetics of zileuton and its conjugated metabolites were evaluated in patients with chronic renal impairment. Five healthy volunteers (creatinine clearance >90 mL/min), five patients with renal failure requiring hemodialysis, six with mild (creatinine clearance, 60–90 mL/min), eight with moderate (creatinine clearance, 30–59 mL/min), and six with severe (creatinine clearance <30 mL/min) renal impairment participated in the study. Zileuton was well tolerated by all participants including those with severe renal impairment and those receiving hemodialysis. The pharmacokinetics of zileuton were similar in healthy volunteers; in patients with mild, moderate and severe renal impairment; and in patients with renal failure requiring hemodialysis. The mean metabolite/parent‐area ratios for the pharmacologically inactive zileuton glucuronides progressively increased with the decline in renal function. A very small percentage of the administered zileuton dose (<0.5%) was removed by hemodialysis. Therefore, adjustment in the dose regimen of zileuton does not appear to be necessary for patients with various degrees of renal impairment and patients with renal failure requiring hemodialysis.</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Female</subject><subject>Humans</subject><subject>Hydroxyurea - administration & dosage</subject><subject>Hydroxyurea - analogs & derivatives</subject><subject>Hydroxyurea - pharmacokinetics</subject><subject>Kidney Diseases - metabolism</subject><subject>Kidney Diseases - physiopathology</subject><subject>Kidney Failure, Chronic - metabolism</subject><subject>Kidney Failure, Chronic - physiopathology</subject><subject>Kidney Failure, Chronic - therapy</subject><subject>Kidney Function Tests</subject><subject>Lipoxygenase Inhibitors - administration & dosage</subject><subject>Lipoxygenase Inhibitors - pharmacokinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Renal Dialysis</subject><subject>Respiratory system</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkE9vEzEQxS0EKqHwEZBWCHHbZWyv7V1OVBFJU1qICgjExRp7varT_RPWjpp--26UVe6cZjTvzRv7R8g7ChkFYB83GRWCpbmEPKNlqbJoIOdUZftnZHaSnpMZQElTpgBeklchbACozAU9I2clFZIrNiO36zscWrT9ve9c9DYkfZ389Y3bxb5LsKuSVQzJjYto-sZHFxLfJWuM3nXj_MHHu-TWddgkq3aLfmjH8WvyosYmuDdTPSe_Fl9-zi_T6-_L1fziOrU5L1RqDIdKmRqEKKEyDgVYLkteC2kUGqyK8WvcOsqsEk4aJitaYAXcYGEcY_ycfDjmbof-386FqFsfrGsa7Fy_C1qVQMuC5aPx09Fohz6EwdV6O_gWh0dNQR-A6o0-UNMHavoAVE9A9X5cfjtd2ZnWVafVieCov590DBabesDO-nCyMVlALovR9vloexjZPv7HA_TVfH15aMeI9BjhQ3T7UwQO91oqroT-_W2pfyz_LBY3S6m_8iev7KLb</recordid><startdate>199705</startdate><enddate>199705</enddate><creator>Awni, Walid M.</creator><creator>Wong, Shekman</creator><creator>Chu, Sou-yie</creator><creator>Patterson, Karen</creator><creator>Hansen, Robert</creator><creator>Machinist, Joseph M.</creator><creator>Drajesk, Jeff</creator><creator>Keane, William F.</creator><creator>Halstenson, Charles E.</creator><general>Blackwell Publishing Ltd</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><scope>7X8</scope></search><sort><creationdate>199705</creationdate><title>Pharmacokinetics of Zileuton and Its Metabolites in Patients with Renal Impairment</title><author>Awni, Walid M. ; Wong, Shekman ; Chu, Sou-yie ; Patterson, Karen ; Hansen, Robert ; Machinist, Joseph M. ; Drajesk, Jeff ; Keane, William F. ; Halstenson, Charles E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4387-bb30d7bf05590dbea50c3693f56b7abad81993ce12c75e6b26d18ad03ba8be223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Female</topic><topic>Humans</topic><topic>Hydroxyurea - administration & dosage</topic><topic>Hydroxyurea - analogs & derivatives</topic><topic>Hydroxyurea - pharmacokinetics</topic><topic>Kidney Diseases - metabolism</topic><topic>Kidney Diseases - physiopathology</topic><topic>Kidney Failure, Chronic - metabolism</topic><topic>Kidney Failure, Chronic - physiopathology</topic><topic>Kidney Failure, Chronic - therapy</topic><topic>Kidney Function Tests</topic><topic>Lipoxygenase Inhibitors - administration & dosage</topic><topic>Lipoxygenase Inhibitors - pharmacokinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Renal Dialysis</topic><topic>Respiratory system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Awni, Walid M.</creatorcontrib><creatorcontrib>Wong, Shekman</creatorcontrib><creatorcontrib>Chu, Sou-yie</creatorcontrib><creatorcontrib>Patterson, Karen</creatorcontrib><creatorcontrib>Hansen, Robert</creatorcontrib><creatorcontrib>Machinist, Joseph M.</creatorcontrib><creatorcontrib>Drajesk, Jeff</creatorcontrib><creatorcontrib>Keane, William F.</creatorcontrib><creatorcontrib>Halstenson, Charles E.</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><collection>MEDLINE - Academic</collection><jtitle>Journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Awni, Walid M.</au><au>Wong, Shekman</au><au>Chu, Sou-yie</au><au>Patterson, Karen</au><au>Hansen, Robert</au><au>Machinist, Joseph M.</au><au>Drajesk, Jeff</au><au>Keane, William F.</au><au>Halstenson, Charles E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics of Zileuton and Its Metabolites in Patients with Renal Impairment</atitle><jtitle>Journal of clinical pharmacology</jtitle><addtitle>J Clin Pharmacol</addtitle><date>1997-05</date><risdate>1997</risdate><volume>37</volume><issue>5</issue><spage>395</spage><epage>404</epage><pages>395-404</pages><issn>0091-2700</issn><eissn>1552-4604</eissn><coden>JCPCBR</coden><abstract>The pharmacokinetics of zileuton and its conjugated metabolites were evaluated in patients with chronic renal impairment. Five healthy volunteers (creatinine clearance >90 mL/min), five patients with renal failure requiring hemodialysis, six with mild (creatinine clearance, 60–90 mL/min), eight with moderate (creatinine clearance, 30–59 mL/min), and six with severe (creatinine clearance <30 mL/min) renal impairment participated in the study. Zileuton was well tolerated by all participants including those with severe renal impairment and those receiving hemodialysis. The pharmacokinetics of zileuton were similar in healthy volunteers; in patients with mild, moderate and severe renal impairment; and in patients with renal failure requiring hemodialysis. The mean metabolite/parent‐area ratios for the pharmacologically inactive zileuton glucuronides progressively increased with the decline in renal function. A very small percentage of the administered zileuton dose (<0.5%) was removed by hemodialysis. Therefore, adjustment in the dose regimen of zileuton does not appear to be necessary for patients with various degrees of renal impairment and patients with renal failure requiring hemodialysis.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>9156372</pmid><doi>10.1002/j.1552-4604.1997.tb04317.x</doi><tpages>10</tpages></addata></record> |
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| subjects | Adult Aged Biological and medical sciences Female Humans Hydroxyurea - administration & dosage Hydroxyurea - analogs & derivatives Hydroxyurea - pharmacokinetics Kidney Diseases - metabolism Kidney Diseases - physiopathology Kidney Failure, Chronic - metabolism Kidney Failure, Chronic - physiopathology Kidney Failure, Chronic - therapy Kidney Function Tests Lipoxygenase Inhibitors - administration & dosage Lipoxygenase Inhibitors - pharmacokinetics Male Medical sciences Middle Aged Pharmacology. Drug treatments Renal Dialysis Respiratory system |
| title | Pharmacokinetics of Zileuton and Its Metabolites in Patients with Renal Impairment |
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