Multiple dose pharmacokinetics of Oral transmucosal fentanyl citrate in healthy volunteers
Oral transmucosal fentanyl citrate (OTFC) is a solid form of fentanyl that delivers the drug through the oral mucosa. The clinical utility of multiple doses of OTFC in the treatment of "breakthrough" cancer pain is under evaluation. The aim of this study was to test the hypothesis that the...
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| Veröffentlicht in: | Anesthesiology (Philadelphia) 2000-03, Vol.92 (3), p.665-673 |
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| container_title | Anesthesiology (Philadelphia) |
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| creator | EGAN, T. D SHARMA, A ASHBURN, M. A KIEVIT, J PACE, N. L STREISAND, J. B |
| description | Oral transmucosal fentanyl citrate (OTFC) is a solid form of fentanyl that delivers the drug through the oral mucosa. The clinical utility of multiple doses of OTFC in the treatment of "breakthrough" cancer pain is under evaluation. The aim of this study was to test the hypothesis that the pharmacokinetics of OTFC do not change with multiple dosing.
Twelve healthy adult volunteers received intravenous fentanyl (15 microg/kg) or OTFC (three consecutive doses of 800 microg) on separate study sessions. Arterial blood samples were collected for determination of fentanyl plasma concentration by radioimmunoassay. The descriptive pharmacokinetic parameters (maximum concentration, minimum concentration, and time to maximum concentration) were identified from the raw data and subjected to a nonparametric analysis of variance. Population pharmacokinetic models for all subjects and separate models for each subject were developed to estimate the pharmacokinetic parameters of fentanyl after multiple OTFC doses.
The shapes of the profiles of plasma concentration versus time for each dose of OTFC were grossly similar. No change was noted for maximum concentration or time to maximum concentration over the three doses, while minimum concentration did show a significantly increasing trend. Terminal half-lives for intravenous fentanyl and OTFC were similar. A two-compartment population pharmacokinetic model adequately represented the central tendency of the data from all subjects. Individual subject data were best described by either two- or three-compartment pharmacokinetic models. These models demonstrated rapid and substantial absorption of OTFC that did not change systematically with time and multiple dosing.
The pharmacokinetics of OTFC were similar among subjects and did not change with multiple dosing. Multiple OTFC dosing regimens within the dosage schedule examined in this study can thus be formulated without concern about nonlinear accumulation. |
| doi_str_mv | 10.1097/00000542-200003000-00009 |
| format | Article |
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Twelve healthy adult volunteers received intravenous fentanyl (15 microg/kg) or OTFC (three consecutive doses of 800 microg) on separate study sessions. Arterial blood samples were collected for determination of fentanyl plasma concentration by radioimmunoassay. The descriptive pharmacokinetic parameters (maximum concentration, minimum concentration, and time to maximum concentration) were identified from the raw data and subjected to a nonparametric analysis of variance. Population pharmacokinetic models for all subjects and separate models for each subject were developed to estimate the pharmacokinetic parameters of fentanyl after multiple OTFC doses.
The shapes of the profiles of plasma concentration versus time for each dose of OTFC were grossly similar. No change was noted for maximum concentration or time to maximum concentration over the three doses, while minimum concentration did show a significantly increasing trend. Terminal half-lives for intravenous fentanyl and OTFC were similar. A two-compartment population pharmacokinetic model adequately represented the central tendency of the data from all subjects. Individual subject data were best described by either two- or three-compartment pharmacokinetic models. These models demonstrated rapid and substantial absorption of OTFC that did not change systematically with time and multiple dosing.
The pharmacokinetics of OTFC were similar among subjects and did not change with multiple dosing. Multiple OTFC dosing regimens within the dosage schedule examined in this study can thus be formulated without concern about nonlinear accumulation.</description><identifier>ISSN: 0003-3022</identifier><identifier>EISSN: 1528-1175</identifier><identifier>DOI: 10.1097/00000542-200003000-00009</identifier><identifier>PMID: 10719944</identifier><identifier>CODEN: ANESAV</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Administration, Oral ; Adolescent ; Adult ; Analgesics ; Analgesics, Opioid - administration & dosage ; Analgesics, Opioid - pharmacokinetics ; Biological and medical sciences ; Female ; Fentanyl - administration & dosage ; Fentanyl - pharmacokinetics ; Half-Life ; Humans ; Injections, Intravenous ; Male ; Medical sciences ; Middle Aged ; Models, Biological ; Mouth Mucosa - metabolism ; Neuropharmacology ; Nonlinear Dynamics ; Pharmacology. Drug treatments ; Population ; Radioimmunoassay</subject><ispartof>Anesthesiology (Philadelphia), 2000-03, Vol.92 (3), p.665-673</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-395060a2bf7c3060e8694d3828d26defb9b9c49977b997f6c562c57bce72b2f13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1289627$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10719944$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>EGAN, T. D</creatorcontrib><creatorcontrib>SHARMA, A</creatorcontrib><creatorcontrib>ASHBURN, M. A</creatorcontrib><creatorcontrib>KIEVIT, J</creatorcontrib><creatorcontrib>PACE, N. L</creatorcontrib><creatorcontrib>STREISAND, J. B</creatorcontrib><title>Multiple dose pharmacokinetics of Oral transmucosal fentanyl citrate in healthy volunteers</title><title>Anesthesiology (Philadelphia)</title><addtitle>Anesthesiology</addtitle><description>Oral transmucosal fentanyl citrate (OTFC) is a solid form of fentanyl that delivers the drug through the oral mucosa. The clinical utility of multiple doses of OTFC in the treatment of "breakthrough" cancer pain is under evaluation. The aim of this study was to test the hypothesis that the pharmacokinetics of OTFC do not change with multiple dosing.
Twelve healthy adult volunteers received intravenous fentanyl (15 microg/kg) or OTFC (three consecutive doses of 800 microg) on separate study sessions. Arterial blood samples were collected for determination of fentanyl plasma concentration by radioimmunoassay. The descriptive pharmacokinetic parameters (maximum concentration, minimum concentration, and time to maximum concentration) were identified from the raw data and subjected to a nonparametric analysis of variance. Population pharmacokinetic models for all subjects and separate models for each subject were developed to estimate the pharmacokinetic parameters of fentanyl after multiple OTFC doses.
The shapes of the profiles of plasma concentration versus time for each dose of OTFC were grossly similar. No change was noted for maximum concentration or time to maximum concentration over the three doses, while minimum concentration did show a significantly increasing trend. Terminal half-lives for intravenous fentanyl and OTFC were similar. A two-compartment population pharmacokinetic model adequately represented the central tendency of the data from all subjects. Individual subject data were best described by either two- or three-compartment pharmacokinetic models. These models demonstrated rapid and substantial absorption of OTFC that did not change systematically with time and multiple dosing.
The pharmacokinetics of OTFC were similar among subjects and did not change with multiple dosing. Multiple OTFC dosing regimens within the dosage schedule examined in this study can thus be formulated without concern about nonlinear accumulation.</description><subject>Administration, Oral</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Analgesics</subject><subject>Analgesics, Opioid - administration & dosage</subject><subject>Analgesics, Opioid - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Female</subject><subject>Fentanyl - administration & dosage</subject><subject>Fentanyl - pharmacokinetics</subject><subject>Half-Life</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Models, Biological</subject><subject>Mouth Mucosa - metabolism</subject><subject>Neuropharmacology</subject><subject>Nonlinear Dynamics</subject><subject>Pharmacology. 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Drug treatments</topic><topic>Population</topic><topic>Radioimmunoassay</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EGAN, T. D</creatorcontrib><creatorcontrib>SHARMA, A</creatorcontrib><creatorcontrib>ASHBURN, M. A</creatorcontrib><creatorcontrib>KIEVIT, J</creatorcontrib><creatorcontrib>PACE, N. L</creatorcontrib><creatorcontrib>STREISAND, J. B</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>Anesthesiology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>EGAN, T. D</au><au>SHARMA, A</au><au>ASHBURN, M. A</au><au>KIEVIT, J</au><au>PACE, N. 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Twelve healthy adult volunteers received intravenous fentanyl (15 microg/kg) or OTFC (three consecutive doses of 800 microg) on separate study sessions. Arterial blood samples were collected for determination of fentanyl plasma concentration by radioimmunoassay. The descriptive pharmacokinetic parameters (maximum concentration, minimum concentration, and time to maximum concentration) were identified from the raw data and subjected to a nonparametric analysis of variance. Population pharmacokinetic models for all subjects and separate models for each subject were developed to estimate the pharmacokinetic parameters of fentanyl after multiple OTFC doses.
The shapes of the profiles of plasma concentration versus time for each dose of OTFC were grossly similar. No change was noted for maximum concentration or time to maximum concentration over the three doses, while minimum concentration did show a significantly increasing trend. Terminal half-lives for intravenous fentanyl and OTFC were similar. A two-compartment population pharmacokinetic model adequately represented the central tendency of the data from all subjects. Individual subject data were best described by either two- or three-compartment pharmacokinetic models. These models demonstrated rapid and substantial absorption of OTFC that did not change systematically with time and multiple dosing.
The pharmacokinetics of OTFC were similar among subjects and did not change with multiple dosing. Multiple OTFC dosing regimens within the dosage schedule examined in this study can thus be formulated without concern about nonlinear accumulation.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>10719944</pmid><doi>10.1097/00000542-200003000-00009</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload |
| subjects | Administration, Oral Adolescent Adult Analgesics Analgesics, Opioid - administration & dosage Analgesics, Opioid - pharmacokinetics Biological and medical sciences Female Fentanyl - administration & dosage Fentanyl - pharmacokinetics Half-Life Humans Injections, Intravenous Male Medical sciences Middle Aged Models, Biological Mouth Mucosa - metabolism Neuropharmacology Nonlinear Dynamics Pharmacology. Drug treatments Population Radioimmunoassay |
| title | Multiple dose pharmacokinetics of Oral transmucosal fentanyl citrate in healthy volunteers |
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