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

• Frequent plasma sampling for monitoring antiepileptic drugs is invasive and costly.
• Equations can predict steady-state PK parameters for drugs with linear PK profile.
• Herein a system of equations are derived to predict lacosamide PK at steady-state.
• Equations were validated against reference PK parameters from clinical trial data.
• With further study, these equations could facilitate drug monitoring in the clinic.

SummaryPurposeFrequent 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.MethodsEquations 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 3–12 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 ≤15% (precision) were considered acceptable for validation.ResultsThirty-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 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 3–12 h 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.ConclusionDerived 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.