FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2040667320> ?p ?o ?g. }

• W2040667320 endingPage "76" @default.
• W2040667320 startingPage "75" @default.
• W2040667320 abstract "Dear Professor Dahlqvist, We read with interest the article by Fliegert et al. published online on May 20 that describes pupillometry as an evaluation tool for pharmacodynamic profiling [1]. We have previously studied the pharmacokinetics of (R,S)-(±)tramadol and (±)-O-demethyltramadol (M1) in relationship to drug-induced miosis, as measured by infrared pupillometry in 21 young healthy volunteers comprising three equally sized groups of CYP2D6 EMs, heterozygous EMs, and PMs [2]. Our data differ from those of Fliegert et al. in that both pharmacokinetics and pharmacodynamics of tramadol are genotype-dependent in the groups of heterozygous and homozygous EMs (Fig. 1). We have analysed our data in relation to genotype in order to uncover correlations between pharmacokinetic parameters of tramadol and M1 with pupillary response. As shown in Fig. 1, the plasma levels of the parent compound in heterozygous EMs are, at all sampling intervals, lower and the production of M1 is delayed, leading to a shift to the right of the M1 plasma concentration–time curve in comparison with homozygous EM subjects. Also, pupillary response differed considerably between homozygous and heterozygous EMs. The mean maximal effect in homozygous EMs occurred at 4 h post dose, in heterozygous EMs at 12 h. In contrast to Fliegert et al., we also observed a small miotic action of the drug in the PM group using static pupillometry. Significant negative correlations (Spearman’s test) between both tramadol Cmax and AUC0–24 vs Emax (rs= −0.39 and −0.51, respectively; p<0.05) and AUC0–24 vs area under the effect–time curve (AUD0–12) (rs=−0.41; p<0.05) were observed. Higher and positive correlations between both the M1 Cmax and AUC0–24 vs Emax (rs=0.59 and 0.55, respectively; p<0.01) and vs AUD0–12 (rs=0.55 and 0.52, respectively; p<0.01) were observed. The correlations of pharmacokinetic parameters of M1 vs pupillary effect were thus somewhat stronger than the respective values for the parent compound, but we found the strongest correlation of metabolic ratio (concentration of tramadol/concentration of M1) at all sampling intervals (2.5–24 h post dose) vs. the effects (rs range 0.85–0.89; p<0.01). This presumably means that the parent compound itself possesses a minor miotic action, which is observable in healthy volunteers. We have observed a longer time to maximal miosis in heterozygous subjects than in homozygous ones. Fliegert et al. reported that the time to maximal effect was 4–10 h for the mixed homozygous and heterozygous EMs and speculated that it was be due to delayed transfer of M1 through the blood–brain barrier. Based on our data, the pharmacokinetic differences between homozygotes and heterozygotes could be the reason for this observation. In our opinion, it is necessary to consider heterozygous and homozygous EMs as two separate groups when assessing the pharmacokinetic and/or pharmacodynamic parameters of tramadol. Moreover, in reality, there exists no subject with a mixed homozygous and heterozygous EM genotype, and heterozygous and homozygous EM subjects in European populations represent groups that account for approximately 40% and 50% of persons, respectively. O. Slanař (*) . J. R. Idle . F. Perlik Clinical Pharmacology Unit, Institute of Pharmacology, First Faculty of Medicine, Charles University, Na Bojisti 1, Praha 2, 120 00, Czech Republic e-mail: oslan@lf1.cuni.cz Tel.: +420-2-24964135 Fax: +420-2-24964133" @default.
• W2040667320 created "2016-06-24" @default.
• W2040667320 creator A5001951129 @default.
• W2040667320 creator A5002168183 @default.
• W2040667320 creator A5032027339 @default.
• W2040667320 creator A5051248160 @default.
• W2040667320 creator A5090549749 @default.
• W2040667320 date "2005-11-08" @default.
• W2040667320 modified "2023-10-18" @default.
• W2040667320 title "CYP2D6 polymorphism, tramadol pharmacokinetics and pupillary response" @default.
• W2040667320 cites W2028116681 @default.
• W2040667320 doi "https://doi.org/10.1007/s00228-005-0039-1" @default.
• W2040667320 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16283276" @default.
• W2040667320 hasPublicationYear "2005" @default.
• W2040667320 type Work @default.
• W2040667320 sameAs 2040667320 @default.
• W2040667320 citedByCount "15" @default.
• W2040667320 countsByYear W20406673202012 @default.
• W2040667320 countsByYear W20406673202015 @default.
• W2040667320 countsByYear W20406673202017 @default.
• W2040667320 countsByYear W20406673202018 @default.
• W2040667320 countsByYear W20406673202021 @default.
• W2040667320 countsByYear W20406673202023 @default.
• W2040667320 crossrefType "journal-article" @default.
• W2040667320 hasAuthorship W2040667320A5001951129 @default.
• W2040667320 hasAuthorship W2040667320A5002168183 @default.
• W2040667320 hasAuthorship W2040667320A5032027339 @default.
• W2040667320 hasAuthorship W2040667320A5051248160 @default.
• W2040667320 hasAuthorship W2040667320A5090549749 @default.
• W2040667320 hasBestOaLocation W20406673202 @default.
• W2040667320 hasConcept C104317684 @default.
• W2040667320 hasConcept C112705442 @default.
• W2040667320 hasConcept C126322002 @default.
• W2040667320 hasConcept C135763542 @default.
• W2040667320 hasConcept C149737253 @default.
• W2040667320 hasConcept C2779777798 @default.
• W2040667320 hasConcept C2780820201 @default.
• W2040667320 hasConcept C33664856 @default.
• W2040667320 hasConcept C526171541 @default.
• W2040667320 hasConcept C54355233 @default.
• W2040667320 hasConcept C55775858 @default.
• W2040667320 hasConcept C62231903 @default.
• W2040667320 hasConcept C71924100 @default.
• W2040667320 hasConcept C86803240 @default.
• W2040667320 hasConcept C98274493 @default.
• W2040667320 hasConceptScore W2040667320C104317684 @default.
• W2040667320 hasConceptScore W2040667320C112705442 @default.
• W2040667320 hasConceptScore W2040667320C126322002 @default.
• W2040667320 hasConceptScore W2040667320C135763542 @default.
• W2040667320 hasConceptScore W2040667320C149737253 @default.
• W2040667320 hasConceptScore W2040667320C2779777798 @default.
• W2040667320 hasConceptScore W2040667320C2780820201 @default.
• W2040667320 hasConceptScore W2040667320C33664856 @default.
• W2040667320 hasConceptScore W2040667320C526171541 @default.
• W2040667320 hasConceptScore W2040667320C54355233 @default.
• W2040667320 hasConceptScore W2040667320C55775858 @default.
• W2040667320 hasConceptScore W2040667320C62231903 @default.
• W2040667320 hasConceptScore W2040667320C71924100 @default.
• W2040667320 hasConceptScore W2040667320C86803240 @default.
• W2040667320 hasConceptScore W2040667320C98274493 @default.
• W2040667320 hasIssue "1" @default.
• W2040667320 hasLocation W20406673201 @default.
• W2040667320 hasLocation W20406673202 @default.
• W2040667320 hasLocation W20406673203 @default.
• W2040667320 hasOpenAccess W2040667320 @default.
• W2040667320 hasPrimaryLocation W20406673201 @default.
• W2040667320 hasRelatedWork W1892095321 @default.
• W2040667320 hasRelatedWork W2024098525 @default.
• W2040667320 hasRelatedWork W2092267763 @default.
• W2040667320 hasRelatedWork W2102899348 @default.
• W2040667320 hasRelatedWork W2110978560 @default.
• W2040667320 hasRelatedWork W2152050780 @default.
• W2040667320 hasRelatedWork W2766361185 @default.
• W2040667320 hasRelatedWork W3084530120 @default.
• W2040667320 hasRelatedWork W3182490938 @default.
• W2040667320 hasRelatedWork W4246764803 @default.
• W2040667320 hasVolume "62" @default.
• W2040667320 isParatext "false" @default.
• W2040667320 isRetracted "false" @default.
• W2040667320 magId "2040667320" @default.
• W2040667320 workType "article" @default.