Remifentanil versus alfentanil : Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers
Remifentanil is an esterase-metabolized opioid with a rapid clearance. The aim of this study was to contrast the pharmacokinetics and pharmacodynamics of remifentanil and alfentanil in healthy, adult male volunteers. Ten volunteers received infusions of remifentanil and alfentanil on separate study...
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Veröffentlicht in: | Anesthesiology (Philadelphia) 1996-04, Vol.84 (4), p.821-833 |
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description | Remifentanil is an esterase-metabolized opioid with a rapid clearance. The aim of this study was to contrast the pharmacokinetics and pharmacodynamics of remifentanil and alfentanil in healthy, adult male volunteers.
Ten volunteers received infusions of remifentanil and alfentanil on separate study sessions using a randomized, open-label crossover design. Arterial blood samples were analyzed to determine drug blood concentrations. The electroencephalogram was employed as the measure of drug effect. The pharmacokinetics were characterized using a moment analysis, a nonlinear mixed effects model (NONMEM) population analysis, and context-sensitive half-time computer simulations. After processing the raw electroencephalogram to obtain the spectral edge parameter, the pharmacodynamics were characterized using an effect compartment, inhibitory maximum effect model.
Pharmacokinetically, the two drugs are similar in terms of steady-state distribution volume (VD(SS)), but remifentanil's central clearance (CLc)) is substantially greater. The NONMEM analysis population pharmacokinetic parameters for remifentanil include a CLc of 2.9 l x min(-1), a VDss of 21.81, and a terminal half-life of 35.1 min. Corresponding NONMEM parameters for alfentanil are 0.36 l x min(-1), 34.11, and 94.5 min. Pharmacodynamically, the drugs are similar in terms of the time required for equilibration between blood and the effect-site concentrations, as evidenced by a T(12)k(e0) for remifentanil of 0.75 min [corrected] and 0.96 min for alfentanil. However, remifentanil is 19 times more potent than alfentanil, with an effective concentration for 50% maximal effect of 19.9 ng x ml(-1) versus 375.9 ng x ml(-1) for alfentanil.
Compared to alfentanil, the high clearance of remifentanil, combined with its small steady-state distribution volume, results in a rapid decline in blood concentration after termination of an infusion. With the exception of remifentanil's nearly 20-times greater potency (30-times if alfentanil partitioning between whole blood and plasma is considered), the drugs are pharmacodynamically similar. |
doi_str_mv | 10.1097/00000542-199604000-00009 |
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Ten volunteers received infusions of remifentanil and alfentanil on separate study sessions using a randomized, open-label crossover design. Arterial blood samples were analyzed to determine drug blood concentrations. The electroencephalogram was employed as the measure of drug effect. The pharmacokinetics were characterized using a moment analysis, a nonlinear mixed effects model (NONMEM) population analysis, and context-sensitive half-time computer simulations. After processing the raw electroencephalogram to obtain the spectral edge parameter, the pharmacodynamics were characterized using an effect compartment, inhibitory maximum effect model.
Pharmacokinetically, the two drugs are similar in terms of steady-state distribution volume (VD(SS)), but remifentanil's central clearance (CLc)) is substantially greater. The NONMEM analysis population pharmacokinetic parameters for remifentanil include a CLc of 2.9 l x min(-1), a VDss of 21.81, and a terminal half-life of 35.1 min. Corresponding NONMEM parameters for alfentanil are 0.36 l x min(-1), 34.11, and 94.5 min. Pharmacodynamically, the drugs are similar in terms of the time required for equilibration between blood and the effect-site concentrations, as evidenced by a T(12)k(e0) for remifentanil of 0.75 min [corrected] and 0.96 min for alfentanil. However, remifentanil is 19 times more potent than alfentanil, with an effective concentration for 50% maximal effect of 19.9 ng x ml(-1) versus 375.9 ng x ml(-1) for alfentanil.
Compared to alfentanil, the high clearance of remifentanil, combined with its small steady-state distribution volume, results in a rapid decline in blood concentration after termination of an infusion. With the exception of remifentanil's nearly 20-times greater potency (30-times if alfentanil partitioning between whole blood and plasma is considered), the drugs are pharmacodynamically similar.</description><identifier>ISSN: 0003-3022</identifier><identifier>EISSN: 1528-1175</identifier><identifier>DOI: 10.1097/00000542-199604000-00009</identifier><identifier>PMID: 8638836</identifier><identifier>CODEN: ANESAV</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Adolescent ; Adult ; Alfentanil - pharmacokinetics ; Alfentanil - pharmacology ; Analgesics ; Analgesics, Opioid - pharmacokinetics ; Biological and medical sciences ; Computer Simulation ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Electroencephalography - drug effects ; Humans ; Male ; Medical sciences ; Models, Biological ; Neuropharmacology ; Pharmacology. Drug treatments ; Piperidines - pharmacokinetics ; Piperidines - pharmacology ; Remifentanil</subject><ispartof>Anesthesiology (Philadelphia), 1996-04, Vol.84 (4), p.821-833</ispartof><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3038313$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8638836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>EGAN, T. D</creatorcontrib><creatorcontrib>MINTO, C. F</creatorcontrib><creatorcontrib>HERMANN, D. J</creatorcontrib><creatorcontrib>BARR, J</creatorcontrib><creatorcontrib>MUIR, K. T</creatorcontrib><creatorcontrib>SHAFER, S. L</creatorcontrib><title>Remifentanil versus alfentanil : Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers</title><title>Anesthesiology (Philadelphia)</title><addtitle>Anesthesiology</addtitle><description>Remifentanil is an esterase-metabolized opioid with a rapid clearance. The aim of this study was to contrast the pharmacokinetics and pharmacodynamics of remifentanil and alfentanil in healthy, adult male volunteers.
Ten volunteers received infusions of remifentanil and alfentanil on separate study sessions using a randomized, open-label crossover design. Arterial blood samples were analyzed to determine drug blood concentrations. The electroencephalogram was employed as the measure of drug effect. The pharmacokinetics were characterized using a moment analysis, a nonlinear mixed effects model (NONMEM) population analysis, and context-sensitive half-time computer simulations. After processing the raw electroencephalogram to obtain the spectral edge parameter, the pharmacodynamics were characterized using an effect compartment, inhibitory maximum effect model.
Pharmacokinetically, the two drugs are similar in terms of steady-state distribution volume (VD(SS)), but remifentanil's central clearance (CLc)) is substantially greater. The NONMEM analysis population pharmacokinetic parameters for remifentanil include a CLc of 2.9 l x min(-1), a VDss of 21.81, and a terminal half-life of 35.1 min. Corresponding NONMEM parameters for alfentanil are 0.36 l x min(-1), 34.11, and 94.5 min. Pharmacodynamically, the drugs are similar in terms of the time required for equilibration between blood and the effect-site concentrations, as evidenced by a T(12)k(e0) for remifentanil of 0.75 min [corrected] and 0.96 min for alfentanil. However, remifentanil is 19 times more potent than alfentanil, with an effective concentration for 50% maximal effect of 19.9 ng x ml(-1) versus 375.9 ng x ml(-1) for alfentanil.
Compared to alfentanil, the high clearance of remifentanil, combined with its small steady-state distribution volume, results in a rapid decline in blood concentration after termination of an infusion. With the exception of remifentanil's nearly 20-times greater potency (30-times if alfentanil partitioning between whole blood and plasma is considered), the drugs are pharmacodynamically similar.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Alfentanil - pharmacokinetics</subject><subject>Alfentanil - pharmacology</subject><subject>Analgesics</subject><subject>Analgesics, Opioid - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Computer Simulation</subject><subject>Cross-Over Studies</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electroencephalography - drug effects</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Biological</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperidines - pharmacokinetics</subject><subject>Piperidines - pharmacology</subject><subject>Remifentanil</subject><issn>0003-3022</issn><issn>1528-1175</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE9LxDAQxYMouq5-BCEH8VZNMk2bepPFf7AgiJ7LbDt1o2lam3Zhv71ZXHYuw_u9xww8xrgUt1IU-Z3YjU5VIosiE2kUyY4UR2wmtTKJlLk-ZrOIIAGh1Bk7D-E7ylyDOWWnJgNjIJux8E6tbciP6K3jGxrCFDi6A7nni67tccDRboj3axxarLof62m0VUz6-gDrrcd2B63na0I3rrcc68mNvEVHfNO5yY8UP1ywkwZdoMv9nrPPp8ePxUuyfHt-XTwsky-ViTGpJaxwVZkmr1a1KuoGFTY1KERIc01NCoLSLEMyWhdCNbkyAFFR7EXLimDObv7v9kP3O1EYy9aGipxDT90UytyIVOZKx-DVPjitWqrLfrAtDtty31L0r_c-hiqWM6CvbDjEQIABCfAHzyh6zA</recordid><startdate>19960401</startdate><enddate>19960401</enddate><creator>EGAN, T. D</creator><creator>MINTO, C. F</creator><creator>HERMANN, D. J</creator><creator>BARR, J</creator><creator>MUIR, K. T</creator><creator>SHAFER, S. L</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>19960401</creationdate><title>Remifentanil versus alfentanil : Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers</title><author>EGAN, T. D ; MINTO, C. F ; HERMANN, D. J ; BARR, J ; MUIR, K. T ; SHAFER, S. L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g260t-d13babc8f7cbd29dfa2afd32aa3475ef430e466ae855902f72833ae8e54251ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Alfentanil - pharmacokinetics</topic><topic>Alfentanil - pharmacology</topic><topic>Analgesics</topic><topic>Analgesics, Opioid - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Computer Simulation</topic><topic>Cross-Over Studies</topic><topic>Dose-Response Relationship, Drug</topic><topic>Electroencephalography - drug effects</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Biological</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperidines - pharmacokinetics</topic><topic>Piperidines - pharmacology</topic><topic>Remifentanil</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EGAN, T. D</creatorcontrib><creatorcontrib>MINTO, C. F</creatorcontrib><creatorcontrib>HERMANN, D. J</creatorcontrib><creatorcontrib>BARR, J</creatorcontrib><creatorcontrib>MUIR, K. T</creatorcontrib><creatorcontrib>SHAFER, S. L</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>EGAN, T. D</au><au>MINTO, C. F</au><au>HERMANN, D. J</au><au>BARR, J</au><au>MUIR, K. T</au><au>SHAFER, S. L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Remifentanil versus alfentanil : Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers</atitle><jtitle>Anesthesiology (Philadelphia)</jtitle><addtitle>Anesthesiology</addtitle><date>1996-04-01</date><risdate>1996</risdate><volume>84</volume><issue>4</issue><spage>821</spage><epage>833</epage><pages>821-833</pages><issn>0003-3022</issn><eissn>1528-1175</eissn><coden>ANESAV</coden><abstract>Remifentanil is an esterase-metabolized opioid with a rapid clearance. The aim of this study was to contrast the pharmacokinetics and pharmacodynamics of remifentanil and alfentanil in healthy, adult male volunteers.
Ten volunteers received infusions of remifentanil and alfentanil on separate study sessions using a randomized, open-label crossover design. Arterial blood samples were analyzed to determine drug blood concentrations. The electroencephalogram was employed as the measure of drug effect. The pharmacokinetics were characterized using a moment analysis, a nonlinear mixed effects model (NONMEM) population analysis, and context-sensitive half-time computer simulations. After processing the raw electroencephalogram to obtain the spectral edge parameter, the pharmacodynamics were characterized using an effect compartment, inhibitory maximum effect model.
Pharmacokinetically, the two drugs are similar in terms of steady-state distribution volume (VD(SS)), but remifentanil's central clearance (CLc)) is substantially greater. The NONMEM analysis population pharmacokinetic parameters for remifentanil include a CLc of 2.9 l x min(-1), a VDss of 21.81, and a terminal half-life of 35.1 min. Corresponding NONMEM parameters for alfentanil are 0.36 l x min(-1), 34.11, and 94.5 min. Pharmacodynamically, the drugs are similar in terms of the time required for equilibration between blood and the effect-site concentrations, as evidenced by a T(12)k(e0) for remifentanil of 0.75 min [corrected] and 0.96 min for alfentanil. However, remifentanil is 19 times more potent than alfentanil, with an effective concentration for 50% maximal effect of 19.9 ng x ml(-1) versus 375.9 ng x ml(-1) for alfentanil.
Compared to alfentanil, the high clearance of remifentanil, combined with its small steady-state distribution volume, results in a rapid decline in blood concentration after termination of an infusion. With the exception of remifentanil's nearly 20-times greater potency (30-times if alfentanil partitioning between whole blood and plasma is considered), the drugs are pharmacodynamically similar.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>8638836</pmid><doi>10.1097/00000542-199604000-00009</doi><tpages>13</tpages></addata></record> |
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source | MEDLINE; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals |
subjects | Adolescent Adult Alfentanil - pharmacokinetics Alfentanil - pharmacology Analgesics Analgesics, Opioid - pharmacokinetics Biological and medical sciences Computer Simulation Cross-Over Studies Dose-Response Relationship, Drug Electroencephalography - drug effects Humans Male Medical sciences Models, Biological Neuropharmacology Pharmacology. Drug treatments Piperidines - pharmacokinetics Piperidines - pharmacology Remifentanil |
title | Remifentanil versus alfentanil : Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers |
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