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The present study was to develop and validate a rapid analytical method of high-performance liquid chromatography with UV (HPLC/UV) detection for the determination of levetiracetam (LEV) concentration in human serum and cerebrospinal fluid (CSF) samples. The newly developed method was used to measure LEV concentration in the serum/CSF of 29 patients with different types of epilepsy; 52% (group I, n = 15) were treated with LEV in monotherapy, 48% (group II, n = 14) were co-administered with other AEDs. Serum and CSF levels of LEV were correlated with patients dosage, concomitant AEDs, therapeutic effect, and adverse drug reactions (ADRs). The calibration curves for serum and CSF were linear in the range 0.5-100 and 0.5-50 mg/L, respectively, with a coefficient correlation (R) value > 0.998 in each case. The quantitation limit was 0.5 mg/L in serum and CSF. The validated method was found to be selective, precise, and accurate. Optimal Cssmin values according to International League Against Epilepsy (12-46 mg/L) were achieved in 40 and 50% of patients in group I and II, and did not correlate with treatment efficacy in 27 and 21% patients, respectively. The ratio of serum LEV to CSF concentration (Kp) after 2 h administration LEV ranged in group I from 0.31 to 0.92 and in group II from 0.18 to 0.65. These findings indicate that the developed simple and rapid HPLC/UV method may be useful for monitoring serum/CSF LEV concentrations in patients receiving standard doses.

Subject of research Therapy drug monitoring under the control of valproic acid (VPA) is now a well-established tool for the treatment of epilepsy. The pharmacokinetic variability of VPA and inter-individual differences in epilepsy type/seizure severity depending on patients’ age determine serum concentration of this drug in an individual patient. The application of the "individual therapeutic concentration" may be a useful indicator taking into account the clinical condition of a patient. Aim. The aim was to compare values of stationary VPA concentrations in terms of dosing and clinical effect monitoring in different age of epileptic patients. Methods Thirty-three patients at age 20-70 years were divided into three groups: I 20-25 years (n = 15), II 26-39 years (n = 9), III 40-70 years (n = 9). Nine patients were treated with VPA in monotherapy, others received VPA with at least one antiepileptic drug (n = 24). Plasma VPA Cssmin were measured, at steady state, using the commercial CEDIA® Valproic Acid II Assay. Results VPA Cssmin values in groups I, II and III were within the therapeutic range: 93%, 56% and 30%; above it: 0%, 33% and 55% and below it: 6%, 22% and 0%, respectively. The percentage of patients with the least frequent seizure was highest in group I (60%) compared to II (54%) and III (44%). The highest frequency of seizures was in group III (25 seizures/week) compared to group I (6.5 seizures/week). The percentage of patients with 1 attack in 1-7 days was comparable in groups: I (13%), II (12%) and III (12%). On the other hand, the percentage of patients free from epileptic seizures (> 1 year) was the highest in group I (53%) compared to group II (44%) and III (22%). Conclusions The reasons for the obtained differences could be drug interactions, nutritional style and the lack of compliance. The unpredictable VPA dose-concentration-clinical effect supports the need to optimize the therapy and define "individual therapeutic concentration". Using it in practice along with patient’s individual indications and clinical condition allows to achieve seizure-free period with good tolerance or optimal seizure control with minimal VPA side-effects.

The anticonvulsant properties of valproic acid (VPA), a branched short-chain fatty acid, were serendipitously discovered in 1963. Since then, therapeutic roles of VPA have increased to include bipolar disorder and migraine prophylaxis, and have more recently been proposed in cancer, Alzheimer's disease, and HIV treatment. Overall, most patients with epilepsy are optimally treated with serum VPA concentrations of 50–100 mg/l. The unpredictable relationship between dose and VPA concentration supports the need to individualize and maintain therapy using therapeutic drug monitoring (TDM). TDM has been used as a tool to optimize treatment of epilepsy for almost 50 years, and while VPA evidence for its usefulness in improving clinical outcome is scarce, TDM continues to play a role in epilepsy management for reasons: (1)physiological changes due to aging, pregnancy, nutritional status, drug interactions, and comorbidities (ie, those involving liver and kidney function) can affect the pharmacokinetics of this drug; (2)treatment is prophylactic and seizures may occur at irregular intervals; (3)signs of toxicity may be insidious and difficult to interpret, especially if there is associated mental handicap or treatment with multiple antiepileptic drugs (AEDs). The chronic, sometimes lifelong therapy makes it particularly important to monitor treatment to reduce long-term adverse effects. These arguments for TDM are valid regardless of the AED involved. This article discusses the basic pharmacokinetic characteristics of conventional anti-epileptic drugs such as VPA. We summarized current clinical practice using TDM. We described the relationships between serum VPA concentration, clinical effect, and adverse drug reactions as well as the reference concentration range. It concluded that a therapeutic decision should not ultimately be based on serum VPA levels alone; other important factors should be considered including an interview with a patient and his medical history, clinical laboratory and pharmacogenetic data, and very importantly, the patient’s individual therapeutic concentration of VPA in serum.

Introduction: Epilepsy is one of the most common diseases of the central nervous system. According to the World Health Organization, it accounts for 1% of the global burden of disease worldwide. Pharmacotherapy remains the primary therapeutic tool in this disease. However, more and more emphasis is placed on approaching this group of patients in an interdisciplinary manner, taking their various needs into account: social, professional, economic or psychological. Attention is also paid to the positive impact of physical activity on the quality of life of patients with epilepsy. The patients with diagnosed epilepsy often complain of a feeling of instability not reflected in standard neurological examination. Early detection of postural control disorders is possible using an objective research tool which is the modified CTSIB test (Clinical Test of Sensory Interaction and Balance). Aim of the study: The aim of the study was to assess the influence of targeted physical therapy on the quality of life among patients with diagnosed epilepsy of unknown etiology using the SF-36 quality of life questionnaire. Materials and methods: The study included 11 professionally active adults with diagnosed generalized epilepsy of unknown etiology, treated at the Department or Outpatient Clinic of Neurology at John Paul II Specialist Hospital in Kraków. Finally, out of the 11 recruited patients (5 women and 6 men), 1 patient was excluded from the study due to a history of craniocerebral trauma. Patients were examined 3 times every month using EEG and the SF-36 quality of life questionnaire. Additionally, between the 2nd and the 3rd month of the pilot study, the study group underwent physical therapy focused on balance disorders using the Biodex SD stabilometric platform. Results: Overall, the quality of life index measured using the SF-36 quality of life questionnaire in the study group improved after the completion of targeted physical therapy. Conclusions: 1. Generalized epilepsy of unknown etiology results in a significant deterioration in the quality of life of patients, which may also be accompanied by disorders of postural control. 2 A targeted program of physiotherapy in the treatment of patients with generalized epilepsy of unknown etiology may has a positive effect on their quality of life. null