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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004766naa a2200397 4500
001oai:DiVA.org:liu-152586
003SwePub
008181109s2018 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1525862 URI
0247 a https://doi.org/10.1002/prp2.4192 DOI
040 a (SwePub)liu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Haage, Pernilla,d 1982-u Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten4 aut0 (Swepub:liu)perha12
2451 0a Enantioselective pharmacokinetics of tramadol and its three main metabolites; impact of CYP2D6, CYP2B6, and CYP3A4 genotype
264 c 2018-07-05
264 1b John Wiley & Sons,c 2018
338 a electronic2 rdacarrier
520 a Tramadol is a complex drug, being metabolized by polymorphic enzymes and administered as a racemate with the (+)- and (-)-enantiomers of the parent compound and metabolites showing different pharmacological effects. The study aimed to simultaneously determine the enantiomer concentrations of tramadol, O-desmethyltramadol, N-desmethyltramadol, and N,O-didesmethyltramadol following a single dose, and elucidate if enantioselective pharmacokinetics is associated with the time following drug intake and if interindividual differences may be genetically explained. Nineteen healthy volunteers were orally administered either 50 or 100 mg tramadol, whereupon blood samples were drawn at 17 occasions. Enantiomer concentrations in whole blood were measured by LC-MS/MS and the CYP2D6,CYP2B6 and CYP3A4 genotype were determined, using the xTAG CYP2D6 Kit, pyrosequencing and real-time PCR, respectively. A positive correlation between the (+)/(-)-enantiomer ratio and time following drug administration was shown for all four enantiomer pairs. The largest increase in enantiomer ratio was observed for N-desmethyltramadol in CYP2D6 extensive and intermediate metabolizers, rising from about two to almost seven during 24 hours following drug intake. CYP2D6 poor metabolizers showed metabolic profiles markedly different from the ones of intermediate and extensive metabolizers, with large area under the concentration curves (AUCs) of the N-desmethyltramadol enantiomers and low corresponding values of the O-desmethyltramadol and N,O-didesmethyltramadol enantiomers, especially of the (+)-enantiomers. Homozygosity of CYP2B6 *5 and *6 indicated a reduced enzyme function, although further studies are required to confirm it. In conclusion, the increase in enantiomer ratios over time might possibly be used to distinguish a recent tramadol intake from a past one. It also implies that, even though (+)-O-desmethyltramadol is regarded the enantiomer most potent in causing adverse effects, one should not investigate the (+)/(-)-enantiomer ratio of O-desmethyltramadol in relation to side effects without consideration for the time that has passed since drug intake.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng
7001 a Kronstrand, Robert,d 1966-u Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten4 aut0 (Swepub:liu)robkr41
7001 a Josefsson, Martin,d 1967-u Linköpings universitet,Kemi,Tekniska fakulteten4 aut0 (Swepub:liu)marjo13
7001 a Calistri, Simonau Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands / Scuola di Scienze della Salute Umana, Università degli studi di Firenze, Florence, Italy4 aut
7001 a van Schaik, Ron H Nu Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands4 aut
7001 a Green, Henrik,d 1975-u Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten4 aut0 (Swepub:liu)hengr89
7001 a Kugelberg, Fredrik,d 1974-u Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten4 aut0 (Swepub:liu)freku57
7102 a Linköpings universitetb Avdelningen för läkemedelsforskning4 org
7730 t Pharmacology Research & Perspectivesd : John Wiley & Sonsg 6:4q 6:4x 2052-1707
8564 u https://doi.org/10.1002/prp2.419y Fulltext
8564 u https://liu.diva-portal.org/smash/get/diva2:1262021/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 u https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/prp2.419
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-152586
8564 8u https://doi.org/10.1002/prp2.419

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