title: Evaluation of a pharmacokinetic interaction between remacemide hydrochloride and phenobarbitone in healthy males.
abstract: OBJECTIVE
  To determine whether there is a pharmacokinetic interaction between the antiepileptic drugs remacemide and phenobarbitone.
  
  
  METHODS
  In a group of 12 healthy adult male volunteers, the single dose and steady-state kinetics of remacemide were each determined twice, once in the absence and once in the presence of phenobarbitone. The effect of 7 days remacemide intake on initial steady-state plasma phenobarbitone concentrations was also investigated.
  
  
  RESULTS
  Apparent remacemide clearance (CL/F) and elimination half-life values were unchanged after 7 days intake of the drug in the absence of phenobarbitone (1.25 +/- 0.32 vs 1.18 +/- 0.22 l kg(-1) h(-1) and 3.29 +/- 0.68 vs 3.62 +/- 0.85 h, respectively). Concomitant administration of remacemide with phenobarbitone resulted in an increase in the estimated CL/F of remacemide (1.25 +/- 0.32 vs 2.09 +/-0.53 l kg-1 h-1), and a decreased remacemide half-life (3.29 +/- 0.68 vs 2.69 +/- 0.33 h). The elimination of the desglycinyl metabolite of remacemide also appeared to be increased after the phenobarbitone intake (half-life 14.72 +/- 2.82 vs 9.61 +/- 5.51 h, AUC 1532 +/- 258 vs 533 +/- 281 ng ml(-1) h). Mean plasma phenobarbitone concentrations rose after 7 days of continuing remacemide intake (12.67 +/- 1.31 vs 13.86 +/- 1.81 microgram ml(-1)).
  
  
  CONCLUSIONS
  Phenobarbitone induced the metabolism of remacemide and that of its desglycinyl metabolite. Remacemide did not induce its own metabolism, but had a modest inhibitory effect on the clearance of phenobarbitone.
authors: AstraZeneca R & D Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK.
authors: W D
authors: WD
authors: Hooper
authors: M J
authors: MJ
authors: Eadie
authors: G E
authors: GE
authors: Blakey
authors: J A
authors: JA
authors: Lockton
authors: M
authors: M
authors: Manun'Ebo
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; C067553:remacemide; D010634:Phenobarbital