Population Pharmacokinetics of propofol : A multicenter study
Target-controlled infusion is an increasingly common type of administration for propofol. This method requires accurate knowledge of pharmacokinetics, including the effects of age and weight. The authors performed a multicenter population analysis to quantitate the effects of covariates. The authors...
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| Veröffentlicht in: | Anesthesiology (Philadelphia) 2000-03, Vol.92 (3), p.727-738 |
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| description | Target-controlled infusion is an increasingly common type of administration for propofol. This method requires accurate knowledge of pharmacokinetics, including the effects of age and weight. The authors performed a multicenter population analysis to quantitate the effects of covariates.
The authors analyzed 4,112 samples of 270 individuals (150 men, 120 women, aged 2-88 yr, weighing 12-100 kg). Population pharmacokinetic modeling was performed using NONMEM (NONMEM Project Group, University of California, San Francisco, CA). Inter- and intraindividual variability was estimated for clearances and volumes. The effects of age, weight, type of administration and sampling site were investigated.
The pharmacokinetics of propofol were best described by a three-compartment model. Weight was found to be a significant covariate for elimination clearance, the two intercompartmental clearances, and the volumes of the central compartment, the shallow peripheral compartment, and the deep peripheral compartment; power functions with exponents smaller than 1 yielded the best results. The estimates of these parameters for a 70-kg adult were 1.44 l/min, 2.25 l/min, 0.92 l/min, 9.3 l, 44.2 l, and 266 l, respectively. For patients older than 60 yr the elimination clearance decreased linearly. The volume of the central compartment decreased with age. For children, all parameters were increased when normalized to body weight. Venous data showed a decreased elimination clearance; bolus data were characterized by increases in the volumes of the central and shallow peripheral compartments and in the rapid distribution clearance (Cl2) and a decrease in the slow distribution clearance (Cl3).
Pharmacokinetics of propofol can be well described by a three-compartment model. Inclusion of age and weight as covariates significantly improved the model. Adjusting pharmacokinetics to the individual patient should improve the precision of target-controlled infusion and may help to broaden the field of application for target-controlled infusion systems. |
| doi_str_mv | 10.1097/00000542-200003000-00017 |
| format | Article |
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The authors analyzed 4,112 samples of 270 individuals (150 men, 120 women, aged 2-88 yr, weighing 12-100 kg). Population pharmacokinetic modeling was performed using NONMEM (NONMEM Project Group, University of California, San Francisco, CA). Inter- and intraindividual variability was estimated for clearances and volumes. The effects of age, weight, type of administration and sampling site were investigated.
The pharmacokinetics of propofol were best described by a three-compartment model. Weight was found to be a significant covariate for elimination clearance, the two intercompartmental clearances, and the volumes of the central compartment, the shallow peripheral compartment, and the deep peripheral compartment; power functions with exponents smaller than 1 yielded the best results. The estimates of these parameters for a 70-kg adult were 1.44 l/min, 2.25 l/min, 0.92 l/min, 9.3 l, 44.2 l, and 266 l, respectively. For patients older than 60 yr the elimination clearance decreased linearly. The volume of the central compartment decreased with age. For children, all parameters were increased when normalized to body weight. Venous data showed a decreased elimination clearance; bolus data were characterized by increases in the volumes of the central and shallow peripheral compartments and in the rapid distribution clearance (Cl2) and a decrease in the slow distribution clearance (Cl3).
Pharmacokinetics of propofol can be well described by a three-compartment model. Inclusion of age and weight as covariates significantly improved the model. Adjusting pharmacokinetics to the individual patient should improve the precision of target-controlled infusion and may help to broaden the field of application for target-controlled infusion systems.</description><identifier>ISSN: 0003-3022</identifier><identifier>EISSN: 1528-1175</identifier><identifier>DOI: 10.1097/00000542-200003000-00017</identifier><identifier>PMID: 10719952</identifier><identifier>CODEN: ANESAV</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging - physiology ; Algorithms ; Anesthetics, Intravenous - administration & dosage ; Anesthetics, Intravenous - pharmacokinetics ; Anesthetics. Neuromuscular blocking agents ; Biological and medical sciences ; Body Weight - physiology ; Child ; Child, Preschool ; Data Interpretation, Statistical ; Female ; Half-Life ; Humans ; Infusions, Intravenous ; Male ; Medical sciences ; Middle Aged ; Models, Biological ; Neuropharmacology ; Pharmacology. Drug treatments ; Population ; Propofol - administration & dosage ; Propofol - pharmacokinetics ; Sex Characteristics</subject><ispartof>Anesthesiology (Philadelphia), 2000-03, Vol.92 (3), p.727-738</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1289379$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10719952$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SCHÜTTLER, J</creatorcontrib><creatorcontrib>IHMSEN, H</creatorcontrib><title>Population Pharmacokinetics of propofol : A multicenter study</title><title>Anesthesiology (Philadelphia)</title><addtitle>Anesthesiology</addtitle><description>Target-controlled infusion is an increasingly common type of administration for propofol. This method requires accurate knowledge of pharmacokinetics, including the effects of age and weight. The authors performed a multicenter population analysis to quantitate the effects of covariates.
The authors analyzed 4,112 samples of 270 individuals (150 men, 120 women, aged 2-88 yr, weighing 12-100 kg). Population pharmacokinetic modeling was performed using NONMEM (NONMEM Project Group, University of California, San Francisco, CA). Inter- and intraindividual variability was estimated for clearances and volumes. The effects of age, weight, type of administration and sampling site were investigated.
The pharmacokinetics of propofol were best described by a three-compartment model. Weight was found to be a significant covariate for elimination clearance, the two intercompartmental clearances, and the volumes of the central compartment, the shallow peripheral compartment, and the deep peripheral compartment; power functions with exponents smaller than 1 yielded the best results. The estimates of these parameters for a 70-kg adult were 1.44 l/min, 2.25 l/min, 0.92 l/min, 9.3 l, 44.2 l, and 266 l, respectively. For patients older than 60 yr the elimination clearance decreased linearly. The volume of the central compartment decreased with age. For children, all parameters were increased when normalized to body weight. Venous data showed a decreased elimination clearance; bolus data were characterized by increases in the volumes of the central and shallow peripheral compartments and in the rapid distribution clearance (Cl2) and a decrease in the slow distribution clearance (Cl3).
Pharmacokinetics of propofol can be well described by a three-compartment model. Inclusion of age and weight as covariates significantly improved the model. Adjusting pharmacokinetics to the individual patient should improve the precision of target-controlled infusion and may help to broaden the field of application for target-controlled infusion systems.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging - physiology</subject><subject>Algorithms</subject><subject>Anesthetics, Intravenous - administration & dosage</subject><subject>Anesthetics, Intravenous - pharmacokinetics</subject><subject>Anesthetics. Neuromuscular blocking agents</subject><subject>Biological and medical sciences</subject><subject>Body Weight - physiology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Data Interpretation, Statistical</subject><subject>Female</subject><subject>Half-Life</subject><subject>Humans</subject><subject>Infusions, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Models, Biological</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Population</subject><subject>Propofol - administration & dosage</subject><subject>Propofol - pharmacokinetics</subject><subject>Sex Characteristics</subject><issn>0003-3022</issn><issn>1528-1175</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1LxDAQhoMo7rr6FyQH8RZNJskmETwsi1-w4B70XNI0xWra1KY97L83iysOvMzXwzAzCGFGbxg16pbuTQogsA94Fsli6gjNmQRNGFPyGM33PcIpwAydpfSZUyW5PkUzRhUzRsIc3W9jPwU7NrHD2w87tNbFr6bzY-MSjjXuh9jHOgZ8h1e4nUKu-270A07jVO3O0UltQ_IXB79A748Pb-tnsnl9elmvNqQHrkdSOi4U5QL00njpwXPKLVXWKSmZKTXoUkotuBKeV7L2YGXlJZOVAAdmafkCXf_Ozet8Tz6NRdsk50OwnY9TKlR-igAqMnh5AKey9VXRD01rh13xd3AGrg6ATc6GerCda9I_B9pwZfgPKEhkgw</recordid><startdate>20000301</startdate><enddate>20000301</enddate><creator>SCHÜTTLER, J</creator><creator>IHMSEN, H</creator><general>Lippincott</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20000301</creationdate><title>Population Pharmacokinetics of propofol : A multicenter study</title><author>SCHÜTTLER, J ; IHMSEN, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p238t-bc3470342869e5e2e303a07ac75519b828b5584374e3d5fe2a5de515d42c296a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aging - physiology</topic><topic>Algorithms</topic><topic>Anesthetics, Intravenous - administration & dosage</topic><topic>Anesthetics, Intravenous - pharmacokinetics</topic><topic>Anesthetics. Neuromuscular blocking agents</topic><topic>Biological and medical sciences</topic><topic>Body Weight - physiology</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Data Interpretation, Statistical</topic><topic>Female</topic><topic>Half-Life</topic><topic>Humans</topic><topic>Infusions, Intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Models, Biological</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Population</topic><topic>Propofol - administration & dosage</topic><topic>Propofol - pharmacokinetics</topic><topic>Sex Characteristics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SCHÜTTLER, J</creatorcontrib><creatorcontrib>IHMSEN, H</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>MEDLINE - Academic</collection><jtitle>Anesthesiology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SCHÜTTLER, J</au><au>IHMSEN, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Population Pharmacokinetics of propofol : A multicenter study</atitle><jtitle>Anesthesiology (Philadelphia)</jtitle><addtitle>Anesthesiology</addtitle><date>2000-03-01</date><risdate>2000</risdate><volume>92</volume><issue>3</issue><spage>727</spage><epage>738</epage><pages>727-738</pages><issn>0003-3022</issn><eissn>1528-1175</eissn><coden>ANESAV</coden><abstract>Target-controlled infusion is an increasingly common type of administration for propofol. This method requires accurate knowledge of pharmacokinetics, including the effects of age and weight. The authors performed a multicenter population analysis to quantitate the effects of covariates.
The authors analyzed 4,112 samples of 270 individuals (150 men, 120 women, aged 2-88 yr, weighing 12-100 kg). Population pharmacokinetic modeling was performed using NONMEM (NONMEM Project Group, University of California, San Francisco, CA). Inter- and intraindividual variability was estimated for clearances and volumes. The effects of age, weight, type of administration and sampling site were investigated.
The pharmacokinetics of propofol were best described by a three-compartment model. Weight was found to be a significant covariate for elimination clearance, the two intercompartmental clearances, and the volumes of the central compartment, the shallow peripheral compartment, and the deep peripheral compartment; power functions with exponents smaller than 1 yielded the best results. The estimates of these parameters for a 70-kg adult were 1.44 l/min, 2.25 l/min, 0.92 l/min, 9.3 l, 44.2 l, and 266 l, respectively. For patients older than 60 yr the elimination clearance decreased linearly. The volume of the central compartment decreased with age. For children, all parameters were increased when normalized to body weight. Venous data showed a decreased elimination clearance; bolus data were characterized by increases in the volumes of the central and shallow peripheral compartments and in the rapid distribution clearance (Cl2) and a decrease in the slow distribution clearance (Cl3).
Pharmacokinetics of propofol can be well described by a three-compartment model. Inclusion of age and weight as covariates significantly improved the model. Adjusting pharmacokinetics to the individual patient should improve the precision of target-controlled infusion and may help to broaden the field of application for target-controlled infusion systems.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>10719952</pmid><doi>10.1097/00000542-200003000-00017</doi><tpages>12</tpages></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload |
| subjects | Adolescent Adult Aged Aged, 80 and over Aging - physiology Algorithms Anesthetics, Intravenous - administration & dosage Anesthetics, Intravenous - pharmacokinetics Anesthetics. Neuromuscular blocking agents Biological and medical sciences Body Weight - physiology Child Child, Preschool Data Interpretation, Statistical Female Half-Life Humans Infusions, Intravenous Male Medical sciences Middle Aged Models, Biological Neuropharmacology Pharmacology. Drug treatments Population Propofol - administration & dosage Propofol - pharmacokinetics Sex Characteristics |
| title | Population Pharmacokinetics of propofol : A multicenter study |
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