title: The Impact of Pharmacokinetic Interactions With Eslicarbazepine Acetate Versus Oxcarbazepine and Carbamazepine in Clinical Practice.
abstract: Eslicarbazepine acetate (ESL) is a new anti-epileptic drug (AED) chemically related to oxcarbazepine (OXC) and carbamazepine (CBZ) and is increasingly used in clinical practice. The purpose of the study was to investigate 2-way pharmacokinetic interactions between ESL and other AEDs as compared to OXC and CBZ.
  
  
  
  Anonymous data regarding age, gender, use of AEDs, daily doses and serum concentration measurements of ESL, OXC, CBZ and lamotrigine (LTG) and other AEDs were retrieved from 2 therapeutic drug monitoring (TDM) databases in Norway. Drugs were categorized according to their known potential for interactions. Concentration/dose (C/D) ratios were calculated.
  
  
  
  Data from 1100 patients were available. The C/D ratios of ESL and OXC were unchanged in combination with enzyme-inducing AEDs or valproate (VPA). The C/D ratio of CBZ decreased by 40% and 22% in combination with other enzyme-inducing AEDs or VPA, respectively, pointing to an increased clearance. ESL demonstrated no significant enzyme-inducing effect on LTG metabolism although there was a 20% and 34% decrease in the C/D ratio of LTG in combination with OXC and CBZ, respectively.
  
  
  
  Possible pharmacokinetic interactions have been studied for ESL as compared to OXC and CBZ. The pharmacokinetics of ESL is not affected by enzyme-inducing AEDs or VPA and does not affect the metabolism of LTG in contrast to OXC and CBZ. The study demonstrates the value of using TDM databases to explore the potential for pharmacokinetic interactions of new AEDs.
authors.affiliation: *Department of Life Sciences and Health, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences; †The National Center for Epilepsy, Sandvika; ‡Department of Pharmacology, Oslo University Hospital; §Department of Neurology, Innlandet Hospital Trust, Lillehammer; ¶Department of Clinical Pharmacology, St. Olavs University Hospital; ‖Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine; and **Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Johannessen Landmark
authors.forename: Torleiv
authors.initials: T
authors.lastname: Svendsen
authors.forename: Jasmin
authors.initials: J
authors.lastname: Dinarevic
authors.forename: Ruben F
authors.initials: RF
authors.lastname: Kufaas
authors.forename: Arne
authors.initials: A
authors.lastname: Reimers
authors.forename: Eylert
authors.initials: E
authors.lastname: Brodtkorb
authors.forename: Arton
authors.initials: A
authors.lastname: Baftiu
authors.forename: Margrete L
authors.initials: ML
authors.lastname: Burns
authors.forename: Svein I
authors.initials: SI
authors.lastname: Johannessen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003984:Dibenzazepines / Q000097:blood* / Q000493:pharmacokinetics*; D004347:Drug Interactions / Q000502:physiology; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D009664:Norway; D000078330:Oxcarbazepine; D014227:Triazines / Q000493:pharmacokinetics; D014635:Valproic Acid / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D003984:Dibenzazepines; D014227:Triazines; D002220:Carbamazepine; D014635:Valproic Acid; C416835:eslicarbazepine acetate; D000077213:Lamotrigine; D000078330:Oxcarbazepine