A system of equations to approximate the pharmacokinetic parameters of lacosamide at steady state from one plasma sample

作者：Cawello Willi^*; Schaefer Carina

来源：Epilepsy Research, 2014, 108(6): 1068-1075.

DOI：10.1016/j.eplepsyres.2014.05.001

• Pharmacokinetics
• Modeling
• Lacosamide
• Equations
• Antiepileptic drug

Purpose: 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 lacosannide, equations can accurately approximate PK parameters from one steady-state plasma sample. %26lt;br%26gt;Methods: Equations were derived to approximate steady-state peak and trough lacosamide plasma concentrations (C-peak,C-ss and C-trough,C-ss, respectively) and area under concentration time curve during dosing interval (AUC(T),(ss)) from one plasma sample. Lacosamide (k(a): similar to 2h(-1); k(e): similar to 0.05 h(-1), corresponding to half-life of 13 h) was calculated to reach C-peak,C-ss after similar to 1 h (t(max,ss)). Equations were validated by comparing approximations to reference PK parameters obtained from single plasma samples drawn 3-12 h 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 %26lt;= 5% (precision) were considered acceptable for validation. %26lt;br%26gt;Results: Thirty-five healthy subjects (12 young males; 11 elderly males, 12 elderly females) received lacosamide 100 mg/day for 4.5 days. Equation-derived PK values were compared to reference mean C-peak,C-ss, C-trough,C-ss and AUC(T,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 3-12 h after lacosamide administration showed correlation (R-2) range of 0.88-0.97 for AUC(T,ss). Correlation range for C-peak,C-ss, and C-trough,C-ss was 0.65-0.87. Error analyses for individual sample comparisons were independent of time. %26lt;br%26gt;Conclusion: Derived equations approximated lacosamide C-peak,C-ss, C-trough,C-ss and AUC(T,ss) using one steady-state plasma sample within validation range. Approximated PK parameters were within accepted validation criteria when compared to reference PK values.

• 出版日期2014-8