## 2 Materials and Methods
### Patients and Data Collection
For blood collection and storage of serum or plasma samples the following procedure was applied: collection of 5 mL of whole blood in a coated Vacutainer tube with a red tip (Becton Dickinson). After blood collection, it was allowed to clot undisturbed at room temperature (usually 15-30 min). The clot was removed by centrifugation at 1000-2000 rpm for 10 min. After centrifugation, the serum was immediately divided into two fractions >200 uL and immediately transferred to polypropylene tubes (not gel tubes) where they were stored in a freezer -70 \({}^{\circ}\)C. For pharmacokinetic analysis, serum concentrations of \begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline \multirow{2}{*}{**ID**} & \multirow{2}{*}{**Subgroup**} & **Renal** & **Age** & **Weight** & **Height** & **Dosing** & **Epileptic** \\  & & **Function** & **(Years)** & **(Kg)** & **(cm)** & **Regimen** & **Activity** \\ \hline
1 & & & Female & 62 & 84 & 165 & 1000 mg BID & \(\pm\) \\ \hline
2 & & & Male & 26 & 70 & 180 & 1000 mg BID & \(\pm\) \\ \hline
3 & & & Female & 72 & 68 & 160 & 1500 mg BID & + \\ \hline
4 & & & Female & 59 & 75 & 165 & 1500 mg BID & + \\ \hline
5 & & & Male & 47 & 80 & 170 & 1000 mg BID & - \\ \hline
6 & & & Male & 75 & 110 & 170 & 1000 mg BID & - \\ \hline
7 & & & Female & 48 & 58 & 160 & 1500 mg BID & \(\pm\) \\ \hline
8 & & & Male & 33 & 80 & 170 & 1000 mg BID & + \\ \hline
9 & & & Male & 33 & 80 & 170 & 1500 mg BID & + \\ \hline
10 & & & Male & 61 & 65 & 160 & 1000 mg BID & - \\ \hline
11 & & & Male & 83 & 65 & 170 & 1000 mg BID & - \\ \hline
12 & & & Female & 45 & 75 & 170 & 1000 mg BID & - \\ \hline
13 & & & kidney injury & & Male & 73 & 65 & 170 & 1500 mg BID & - \\ \hline
14 & & & Female & 82 & 50 & 150 & 1000 mg BID & - \\ \hline \hline \end{tabular}  
* no activity, \(\pm\) possible, + epileptic activity; BID, twice daily; eGFR, estimated glomerular filtration rate; Stable renal function, when eGFR > 60 mL/min/1.73 m\({}^{2}\).  
\end{table} 
Table 1: Patients’ demographic characteristics, levetiracetam dosing regimen, epileptic activity, and subgroup classification. levetiracetam were determined by high performance liquid chromatography using a UV detector at 205 nm after sample preparation by solid phase extraction using ClinRep(r)HPLC Complete Kit, levetiracetam (Keppra(r)) in serum/plasma (order number 15500) (RECIPE Chemicals & Instruments GmbH, Munich, Germany). The lower limit of detection was 0.14 mg/L, the lower limit of quantification was 0.46 mg/L, the upper quantification limit was 104 mg/L, and the recovery was 97-105%. The chromatographic test was performed with the ClinTest(r) standard solution, calibration with the ClinCal(r) serum calibrator and quality control with the ClinChek(r) serum controls level I & II test solutions (order number 15582). The precision of the method was determined by calculating the relative standard deviation at three plasma concentrations during the same analysis (within-day precision) and in triplicate over six analyses (between-day precision). For the entire concentration range, the relative standard errors for both within- and between-assay precision were less than 7.2%.