title: Single and multiple dose pharmacokinetics of felbamate in the elderly.
abstract: OBJECTIVE
  The objective of this study was to compare the pharmacokinetics, safety and tolerability of the antiepileptic drug felbamate in young and elderly healthy vounteers.
  
  
  METHODS
  The single and multiple dose pharmacokinetics of felbamate were examined in an open-label two-dose level parallel group study in 24 elderly (66 to 78-year-old) and 11 young (18 to 45-year-old) healthy volunteer subjects. Pharmacokinetics were determined from blood samples obtained over 120 h after administration of single 600 mg or 1200 mg doses, and after multiple doses of 600 mg or 1200 mg administered every 12 h. Safety and tolerability were assessed through laboratory tests, ECGs, vital signs and reported adverse events.
  
  
  RESULTS
  Single dose felbamate pharmacokinetic parameters differed between young and elderly subjects; compared with young subjects, elderly subjects had lower mean clearance (31.2 vs 25.1 ml min(-1); 90% CI -11.4 to -0.9; P = 0.02) and a trend towards a greater half-life (18.6 vs 21.0 h; 90% CI -0.6 to 5.4; P = 0.11). Mean AUC and C(max) values were also higher in elderly subjects. No gender differences were noted for weight-adjusted pharmacokinetic variables. Felbamate was less well tolerated in elderly subjects compared with young subjects, as shown by higher rates of adverse event reporting and dropouts at the higher dose level. This may be due to age-related pharmacokinetic differences, to the rapid dose titration schedule used in this study, and/or to altered sensitivity to felbamate's pharmacodynamic effects.
  
  
  CONCLUSIONS
  These findings imply that elderly subjects require lower initial dosing and slower dose titration of felbamate than non-elderly subjects.
authors.affiliation: Cardiff Clinical Trials, Wales.
authors.forename: A
authors.initials: A
authors.lastname: Richens
authors.forename: C R
authors.initials: CR
authors.lastname: Banfield
authors.forename: M
authors.initials: M
authors.lastname: Salfi
authors.forename: A
authors.initials: A
authors.lastname: Nomeir
authors.forename: C C
authors.initials: CC
authors.lastname: Lin
authors.forename: P
authors.initials: P
authors.lastname: Jensen
authors.forename: M B
authors.initials: MB
authors.lastname: Affrime
authors.forename: P
authors.initials: P
authors.lastname: Glue
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D000078328:Felbamate; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012016:Reference Values
chemical_list: D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D000078328:Felbamate