The pharmacokinetics of ketobemidone are not affected by CYP2D6 or CYP2C19 phenotype
The pharmacokinetics of orally administered ketobemidone were investigated in three groups of healthy volunteers with respect to cytochrome P450 (CYP) 2D6 and CYP2C19 phenotypes: extensive metabolisers (EMs) of debrisoquine and mephenytoin (EMdeb/EMmeph), poor metabolisers (PMs) of debrisoquine (PMd...
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description | The pharmacokinetics of orally administered ketobemidone were investigated in three groups of healthy volunteers with respect to cytochrome P450 (CYP) 2D6 and CYP2C19 phenotypes: extensive metabolisers (EMs) of debrisoquine and mephenytoin (EMdeb/EMmeph), poor metabolisers (PMs) of debrisoquine (PMdeb/EMmeph) and poor metabolisers of mephenytoin (PMmeph/EMdeb). Peak plasma concentration, oral clearance, area under the plasma concentration-time curve, half-life, volume of distribution and mean residence time were not significantly different among the three groups. There was no correlation between oral clearance of ketobemidone and debrisoquine or mephenytoin metabolic ratios. Further, the urinary excretion of ketobemidone and norketobemidone was not affected by the phenotype for either CYP2D6 or CYP2C19. However, a substantial variation in plasma concentration was observed within all three groups. The results indicate that the metabolism of ketobemidone is not dependent on CYP2D6 or CYP2C19. PMs of debrisoquine or mephenytoin, as well as patients who are concomitantly treated with inhibitors of CYP2D6 or CYP2C19, are not expected to be at higher risk of adverse effects. However, due to the interindividual variability in plasma levels of ketobemidone, independent of phenotype, individual dosing based on the clinical response and therapeutic drug monitoring is recommended. |
doi_str_mv | 10.1007/s00228-001-0413-6 |
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Peak plasma concentration, oral clearance, area under the plasma concentration-time curve, half-life, volume of distribution and mean residence time were not significantly different among the three groups. There was no correlation between oral clearance of ketobemidone and debrisoquine or mephenytoin metabolic ratios. Further, the urinary excretion of ketobemidone and norketobemidone was not affected by the phenotype for either CYP2D6 or CYP2C19. However, a substantial variation in plasma concentration was observed within all three groups. The results indicate that the metabolism of ketobemidone is not dependent on CYP2D6 or CYP2C19. PMs of debrisoquine or mephenytoin, as well as patients who are concomitantly treated with inhibitors of CYP2D6 or CYP2C19, are not expected to be at higher risk of adverse effects. However, due to the interindividual variability in plasma levels of ketobemidone, independent of phenotype, individual dosing based on the clinical response and therapeutic drug monitoring is recommended.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/s00228-001-0413-6</identifier><identifier>PMID: 11936707</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Adult ; Analgesics ; Analgesics, Opioid - pharmacokinetics ; Aryl Hydrocarbon Hydroxylases ; Biological and medical sciences ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP2D6 - physiology ; Cytochrome P-450 Enzyme System - physiology ; Female ; Humans ; Male ; Medical sciences ; Meperidine - analogs & derivatives ; Meperidine - pharmacokinetics ; Mixed Function Oxygenases - physiology ; Mouth Mucosa - metabolism ; Neuropharmacology ; Neurotransmitters. Neurotransmission. 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Drug treatments</subject><ispartof>European journal of clinical pharmacology, 2002-02, Vol.57 (12), p.877-881</ispartof><rights>2002 INIST-CNRS</rights><rights>Springer-Verlag 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-6916c64b5434f51bf17f5ddbb967316ea820d7254e262f0e15117be339d4f1e83</citedby></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=13527861$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11936707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>AL-SHURBAJI, Ayman</creatorcontrib><creatorcontrib>SÄWE, Juliette</creatorcontrib><title>The pharmacokinetics of ketobemidone are not affected by CYP2D6 or CYP2C19 phenotype</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><description>The pharmacokinetics of orally administered ketobemidone were investigated in three groups of healthy volunteers with respect to cytochrome P450 (CYP) 2D6 and CYP2C19 phenotypes: extensive metabolisers (EMs) of debrisoquine and mephenytoin (EMdeb/EMmeph), poor metabolisers (PMs) of debrisoquine (PMdeb/EMmeph) and poor metabolisers of mephenytoin (PMmeph/EMdeb). Peak plasma concentration, oral clearance, area under the plasma concentration-time curve, half-life, volume of distribution and mean residence time were not significantly different among the three groups. There was no correlation between oral clearance of ketobemidone and debrisoquine or mephenytoin metabolic ratios. Further, the urinary excretion of ketobemidone and norketobemidone was not affected by the phenotype for either CYP2D6 or CYP2C19. However, a substantial variation in plasma concentration was observed within all three groups. The results indicate that the metabolism of ketobemidone is not dependent on CYP2D6 or CYP2C19. PMs of debrisoquine or mephenytoin, as well as patients who are concomitantly treated with inhibitors of CYP2D6 or CYP2C19, are not expected to be at higher risk of adverse effects. However, due to the interindividual variability in plasma levels of ketobemidone, independent of phenotype, individual dosing based on the clinical response and therapeutic drug monitoring is recommended.</description><subject>Adult</subject><subject>Analgesics</subject><subject>Analgesics, Opioid - pharmacokinetics</subject><subject>Aryl Hydrocarbon Hydroxylases</subject><subject>Biological and medical sciences</subject><subject>Cytochrome P-450 CYP2C19</subject><subject>Cytochrome P-450 CYP2D6 - physiology</subject><subject>Cytochrome P-450 Enzyme System - physiology</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Meperidine - analogs & derivatives</subject><subject>Meperidine - pharmacokinetics</subject><subject>Mixed Function Oxygenases - physiology</subject><subject>Mouth Mucosa - metabolism</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems</subject><subject>Pharmacology. 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Neurotransmission. Receptors</topic><topic>Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>AL-SHURBAJI, Ayman</creatorcontrib><creatorcontrib>SÄWE, Juliette</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>AL-SHURBAJI, Ayman</au><au>SÄWE, Juliette</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The pharmacokinetics of ketobemidone are not affected by CYP2D6 or CYP2C19 phenotype</atitle><jtitle>European journal of clinical pharmacology</jtitle><addtitle>Eur J Clin Pharmacol</addtitle><date>2002-02-01</date><risdate>2002</risdate><volume>57</volume><issue>12</issue><spage>877</spage><epage>881</epage><pages>877-881</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>The pharmacokinetics of orally administered ketobemidone were investigated in three groups of healthy volunteers with respect to cytochrome P450 (CYP) 2D6 and CYP2C19 phenotypes: extensive metabolisers (EMs) of debrisoquine and mephenytoin (EMdeb/EMmeph), poor metabolisers (PMs) of debrisoquine (PMdeb/EMmeph) and poor metabolisers of mephenytoin (PMmeph/EMdeb). Peak plasma concentration, oral clearance, area under the plasma concentration-time curve, half-life, volume of distribution and mean residence time were not significantly different among the three groups. There was no correlation between oral clearance of ketobemidone and debrisoquine or mephenytoin metabolic ratios. Further, the urinary excretion of ketobemidone and norketobemidone was not affected by the phenotype for either CYP2D6 or CYP2C19. However, a substantial variation in plasma concentration was observed within all three groups. The results indicate that the metabolism of ketobemidone is not dependent on CYP2D6 or CYP2C19. PMs of debrisoquine or mephenytoin, as well as patients who are concomitantly treated with inhibitors of CYP2D6 or CYP2C19, are not expected to be at higher risk of adverse effects. 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subjects | Adult Analgesics Analgesics, Opioid - pharmacokinetics Aryl Hydrocarbon Hydroxylases Biological and medical sciences Cytochrome P-450 CYP2C19 Cytochrome P-450 CYP2D6 - physiology Cytochrome P-450 Enzyme System - physiology Female Humans Male Medical sciences Meperidine - analogs & derivatives Meperidine - pharmacokinetics Mixed Function Oxygenases - physiology Mouth Mucosa - metabolism Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments |
title | The pharmacokinetics of ketobemidone are not affected by CYP2D6 or CYP2C19 phenotype |
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