Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients
The pharmacokinetics of midazolam and of its main metabolite, 1-hydroxymidazolam, were investigated in intensive care patients after intravenous bolus of 0.2 mg/kg followed by a 0.1 mg/kg/h intravenous infusion of midazolam over 2 hours. A wide interpatient variability of the main pharmacokinetic pa...
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| Veröffentlicht in: | European journal of drug metabolism and pharmacokinetics 1998-04, Vol.23 (2), p.255-258 |
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| container_title | European journal of drug metabolism and pharmacokinetics |
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| creator | BOULIEU, R LEHMANN, B SALORD, F FISHER, C MORLET, D |
| description | The pharmacokinetics of midazolam and of its main metabolite, 1-hydroxymidazolam, were investigated in intensive care patients after intravenous bolus of 0.2 mg/kg followed by a 0.1 mg/kg/h intravenous infusion of midazolam over 2 hours. A wide interpatient variability of the main pharmacokinetic parameters of midazolam was found. The mean values of elimination half life and volume of distribution, 4.5 +/- 5.4 h and 1.7 +/- 0.7 l/kg respectively, were higher than those reported in healthy subjects. Total plasma clearance was significantly increased in patients taking drugs that induce hepatic metabolism. Significant concentrations of the unconjugated form of 1-hydroxymidazolam were recovered in plasma. The volume of distribution and the elimination half life of the metabolite were higher than those of the parent drug. These results show that 1-hydroxymidazolam might contribute to the pharmacodynamic effect of midazolam and consequently must be taken into account during pharmacokinetic and pharmacodynamic studies. |
| doi_str_mv | 10.1007/BF03189348 |
| format | Article |
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A wide interpatient variability of the main pharmacokinetic parameters of midazolam was found. The mean values of elimination half life and volume of distribution, 4.5 +/- 5.4 h and 1.7 +/- 0.7 l/kg respectively, were higher than those reported in healthy subjects. Total plasma clearance was significantly increased in patients taking drugs that induce hepatic metabolism. Significant concentrations of the unconjugated form of 1-hydroxymidazolam were recovered in plasma. The volume of distribution and the elimination half life of the metabolite were higher than those of the parent drug. These results show that 1-hydroxymidazolam might contribute to the pharmacodynamic effect of midazolam and consequently must be taken into account during pharmacokinetic and pharmacodynamic studies.</description><identifier>ISSN: 0378-7966</identifier><identifier>EISSN: 2107-0180</identifier><identifier>DOI: 10.1007/BF03189348</identifier><identifier>PMID: 9725490</identifier><language>eng</language><publisher>Genève: Médecine et hygiène</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Critical Care ; Female ; Humans ; Hypnotics and Sedatives - metabolism ; Hypnotics and Sedatives - pharmacokinetics ; Hypnotics. Sedatives ; Injections, Intravenous ; Male ; Medical sciences ; Midazolam - analogs & derivatives ; Midazolam - metabolism ; Midazolam - pharmacokinetics ; Middle Aged ; Neuropharmacology ; Pharmacology. Drug treatments ; Psychology. Psychoanalysis. 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A wide interpatient variability of the main pharmacokinetic parameters of midazolam was found. The mean values of elimination half life and volume of distribution, 4.5 +/- 5.4 h and 1.7 +/- 0.7 l/kg respectively, were higher than those reported in healthy subjects. Total plasma clearance was significantly increased in patients taking drugs that induce hepatic metabolism. Significant concentrations of the unconjugated form of 1-hydroxymidazolam were recovered in plasma. The volume of distribution and the elimination half life of the metabolite were higher than those of the parent drug. These results show that 1-hydroxymidazolam might contribute to the pharmacodynamic effect of midazolam and consequently must be taken into account during pharmacokinetic and pharmacodynamic studies.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Critical Care</subject><subject>Female</subject><subject>Humans</subject><subject>Hypnotics and Sedatives - metabolism</subject><subject>Hypnotics and Sedatives - pharmacokinetics</subject><subject>Hypnotics. Sedatives</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Midazolam - analogs & derivatives</subject><subject>Midazolam - metabolism</subject><subject>Midazolam - pharmacokinetics</subject><subject>Middle Aged</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Psychology. 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Psychiatry</subject><subject>Psychopharmacology</subject><issn>0378-7966</issn><issn>2107-0180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkDtLBDEURoMouug29kIKsRBG85g8plTxBQtaaD3cydxgdB5rkhXXX--Ii97mFt_hFIeQQ87OOGPm_PKGSW4rWdotMhOcmYJxy7bJjEljC1NpvUfmKb2y6aStlNK7ZLcyQpUVmxH3-AKxBze-hQFzcImOnvahha-xg57C0NKQE-0hDLTHDM3YhYyUFy_rNo6f6390AsKQcUjhA6mDiHQJOeCQ0wHZ8dAlnG_-Pnm-uX66uisWD7f3VxeLwknOcyF00yjhdQPSeq2sdiCNtkY1pfRWaFNykByBazRYalWJRqH3FlC20hsu98nJr3cZx_cVplz3ITnsOhhwXKXayEk2JZvA01_QxTGliL5extBDXNec1T9R6_-oE3y0sa6aHts_dJNw2o83OyQHnY8wuJD-MFEKJQyT3w9PfrU</recordid><startdate>19980401</startdate><enddate>19980401</enddate><creator>BOULIEU, R</creator><creator>LEHMANN, B</creator><creator>SALORD, F</creator><creator>FISHER, C</creator><creator>MORLET, D</creator><general>Médecine et hygiène</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>19980401</creationdate><title>Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients</title><author>BOULIEU, R ; LEHMANN, B ; SALORD, F ; FISHER, C ; MORLET, D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c311t-26bb52f6ba38f6586ca376875b43f826741a31ea16e7e46592b5eff8ae3d3f713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Critical Care</topic><topic>Female</topic><topic>Humans</topic><topic>Hypnotics and Sedatives - metabolism</topic><topic>Hypnotics and Sedatives - pharmacokinetics</topic><topic>Hypnotics. Sedatives</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Midazolam - analogs & derivatives</topic><topic>Midazolam - metabolism</topic><topic>Midazolam - pharmacokinetics</topic><topic>Middle Aged</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BOULIEU, R</creatorcontrib><creatorcontrib>LEHMANN, B</creatorcontrib><creatorcontrib>SALORD, F</creatorcontrib><creatorcontrib>FISHER, C</creatorcontrib><creatorcontrib>MORLET, D</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>European journal of drug metabolism and pharmacokinetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BOULIEU, R</au><au>LEHMANN, B</au><au>SALORD, F</au><au>FISHER, C</au><au>MORLET, D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients</atitle><jtitle>European journal of drug metabolism and pharmacokinetics</jtitle><addtitle>Eur J Drug Metab Pharmacokinet</addtitle><date>1998-04-01</date><risdate>1998</risdate><volume>23</volume><issue>2</issue><spage>255</spage><epage>258</epage><pages>255-258</pages><issn>0378-7966</issn><eissn>2107-0180</eissn><abstract>The pharmacokinetics of midazolam and of its main metabolite, 1-hydroxymidazolam, were investigated in intensive care patients after intravenous bolus of 0.2 mg/kg followed by a 0.1 mg/kg/h intravenous infusion of midazolam over 2 hours. A wide interpatient variability of the main pharmacokinetic parameters of midazolam was found. The mean values of elimination half life and volume of distribution, 4.5 +/- 5.4 h and 1.7 +/- 0.7 l/kg respectively, were higher than those reported in healthy subjects. Total plasma clearance was significantly increased in patients taking drugs that induce hepatic metabolism. Significant concentrations of the unconjugated form of 1-hydroxymidazolam were recovered in plasma. The volume of distribution and the elimination half life of the metabolite were higher than those of the parent drug. These results show that 1-hydroxymidazolam might contribute to the pharmacodynamic effect of midazolam and consequently must be taken into account during pharmacokinetic and pharmacodynamic studies.</abstract><cop>Genève</cop><pub>Médecine et hygiène</pub><pmid>9725490</pmid><doi>10.1007/BF03189348</doi><tpages>4</tpages></addata></record> |
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| identifier | ISSN: 0378-7966 |
| ispartof | European journal of drug metabolism and pharmacokinetics, 1998-04, Vol.23 (2), p.255-258 |
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| subjects | Adolescent Adult Aged Aged, 80 and over Biological and medical sciences Critical Care Female Humans Hypnotics and Sedatives - metabolism Hypnotics and Sedatives - pharmacokinetics Hypnotics. Sedatives Injections, Intravenous Male Medical sciences Midazolam - analogs & derivatives Midazolam - metabolism Midazolam - pharmacokinetics Middle Aged Neuropharmacology Pharmacology. Drug treatments Psychology. Psychoanalysis. Psychiatry Psychopharmacology |
| title | Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients |
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