title: Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy.
abstract: OBJECTIVE
  Pregabalin (PGB) is an alpha2-delta ligand with demonstrated efficacy in epilepsy, neuropathic pain, and anxiety disorders. PGB is highly efficacious as adjunctive therapy in patients with refractory partial seizures.
  
  
  METHODS
  Given its efficacy as adjunctive therapy, the potential for interaction of PGB with other antiepileptic drugs (AEDs) was assessed in patients with partial epilepsy in open-label, multiple-dose studies. Patients received PGB, 600 mg/day (200 mg q8h) for 7 days, in combination with their individualized maintenance monotherapy with valproate (VPA), phenytoin (PHT), lamotrigine (LTG), or carbamazepine (CBZ).
  
  
  RESULTS
  Trough steady-state concentrations of CBZ (and its epoxide metabolite), PHT, LTG, and VPA were unaffected by concomitant PGB administration. Likewise, PGB steady-state pharmacokinetic parameter values were similar among patients receiving CBZ, PHT, LTG, or VPA and, in general, were similar to those observed historically in healthy subjects receiving PGB alone. The PGB-AED combinations were generally well tolerated. PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug-drug interactions.
authors.affiliation: Pfizer, Global Research and Development, Ann Arbor, Michigan 48105, USA.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Brodie
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Wilson
authors.forename: David L
authors.initials: DL
authors.lastname: Wesche
authors.forename: Christine W
authors.initials: CW
authors.lastname: Alvey
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Randinitis
authors.forename: Edward L
authors.initials: EL
authors.lastname: Posvar
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Hounslow
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Bron
authors.forename: G L
authors.initials: GL
authors.lastname: Gibson
authors.forename: Howard N
authors.initials: HN
authors.lastname: Bockbrader
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D002220:Carbamazepine / Q000493:pharmacokinetics; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000493:pharmacokinetics; D000069583:Pregabalin; D014227:Triazines / Q000493:pharmacokinetics; D014635:Valproic Acid / Q000493:pharmacokinetics; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D010672:Phenytoin; D000077213:Lamotrigine