title: A system of equations to approximate the pharmacokinetic parameters of lacosamide at steady state from one plasma sample.
abstract: OBJECTIVE
  Frequent plasma sampling to monitor pharmacokinetic (PK) profile of antiepileptic drugs (AEDs), is invasive, costly and time consuming. For drugs with a well-defined PK profile, such as AED lacosamide, equations can accurately approximate PK parameters from one steady-state plasma sample.
  
  
  METHODS
  Equations were derived to approximate steady-state peak and trough lacosamide plasma concentrations (Cpeak,ss and Ctrough,ss, respectively) and area under concentration-time curve during dosing interval (AUCτ,ss) from one plasma sample. Lacosamide (ka: ∼2 h(-1); ke: ∼0.05 h(-1), corresponding to half-life of 13 h) was calculated to reach Cpeak,ss after ∼1 h (tmax,ss). Equations were validated by comparing approximations to reference PK parameters obtained from single plasma samples drawn 3-12h following lacosamide administration, using data from double-blind, placebo-controlled, parallel-group PK study. Values of relative bias (accuracy) between -15% and +15%, and root mean square error (RMSE) values≤15% (precision) were considered acceptable for validation.
  
  
  RESULTS
  Thirty-five healthy subjects (12 young males; 11 elderly males, 12 elderly females) received lacosamide 100mg/day for 4.5 days. Equation-derived PK values were compared to reference mean Cpeak,ss, Ctrough,ss and AUCτ,ss values. Equation-derived PK data had a precision of 6.2% and accuracy of -8.0%, 2.9%, and -0.11%, respectively. Equation-derived versus reference PK values for individual samples obtained 3-12h after lacosamide administration showed correlation (R2) range of 0.88-0.97 for AUCτ,ss. Correlation range for Cpeak,ss and Ctrough,ss was 0.65-0.87. Error analyses for individual sample comparisons were independent of time.
  
  
  CONCLUSIONS
  Derived equations approximated lacosamide Cpeak,ss, Ctrough,ss and AUCτ,ss using one steady-state plasma sample within validation range. Approximated PK parameters were within accepted validation criteria when compared to reference PK values.
authors.affiliation: UCB Pharma, Global Statistical Science, D-40789 Monheim, Germany. Electronic address: willi.cawello@ucb.com.
authors.forename: Willi
authors.initials: W
authors.lastname: Cawello
authors.affiliation: UCB Pharma, Global Statistical Science, D-40789 Monheim, Germany; University Düsseldorf, Institute of Clinical Pharmacy and Pharmacotherapy, D-40225 Düsseldorf, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Schäfer
mesh_terms: D000081:Acetamides / Q000097:blood* / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000465:Algorithms; D000927:Anticonvulsants / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018849:Controlled Clinical Trials as Topic; D005260:Female; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008954:Models, Biological
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide
keywords: Antiepileptic drug; Equations; Lacosamide; Modeling; Pharmacokinetics