Introduction Levetiracetam is a relatively new anti-ep-ileptic drug (AED), indicated as an adjunctive therapy for partial-onset seizures and primary generalised tonic-clon-ic seizures in adults and children. However, information about the influence of altered pharmacokinetics during pregnancy on levetiracetam dose, serum concentration and clinical efficacy is still limited. This study aims to de-scribe the relation between certain parameters of preg-nant women and levetiracetam blood levels in different stages of pregnancy.
Methods Pregnant women treated with levetiracetam for epilepsy from neurology clinics in several medical centres were followed in this study. Trough blood sam-ples were obtained (therapeutic range: 10–37 mg/L) at dif-ferent stages of pregnancy, while sampling frequency for each woman was decided by the neurologist. Levetiracetam dose, pregnancy week, and seizure occurrence were recorded, and levetiracetam blood concentrations were quantified using HPLC-based method. These data were analysed in order to reveal the changes in levetiracetam blood concentrations before and during pregnancy, and their potential clinical implications.
Results Fifty two pregnant women treated with leveti-racetam for epilepsy participated in this study. In many of these patients, levetiracetam plasma concentrations decreased during pregnancy, and the drug dose was in-creased gradually to maintain the concentrations in the therapeutic range. Despite this, levetiracetam plasma concentrations were below and above the therapeutic range in 41% and 5.5% of the collected samples, respec-tively. Based on the dose-normalised levetiracetam plas-ma concentrations, exposure to a given dose of the drug decreases by approximately 35% during the first trimester, and stays reduced over the 2nd and 3rd trimesters. Overall, many patients were exposed to sub-therapeutic leveti-racetam plasma concentrations during substantial parts of pregnancy. However, no clear correlation between the levetiracetam plasma concentrations and occurrence of seizures was identified.
Conclusion Levetiracetam blood concentrations tend to decrease during pregnancy as opposed to pre-preg-nancy state, apparently due to increased drug clearance. As a result, levetiracetam blood concentrations during pregnancy may decline below the therapeutic range, leading to a higher risk of seizures. Therefore, monitoring of levetiracetam blood concentrations during pregnan-cy is needed to maintain therapeutic concentrations via gradual increase in drug doses. More detailed analysis is needed to reveal the pregnancy-related changes in the levetiracetam pharmacokinetics (clearance) and pharma-codynamics.
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