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Prospective study on concentration-efficacy and concentration-toxicity: correlations with lamotrigine serum levels
Walter Fröscher1, Ferdinand Keller, Heinrich Vogt
1Department of Neurology and Epileptology, Weissenau, Ravensburg, Germany. walter.froescher@zfp-weissenau.de
Rationale:
The relationship between lamotrigine (LTG) serum concentration and clinical response in patients with epilepsy is still controversial. We therefore performed a prospective study in which LTG was added to the existing therapeutic regimen in patients with poorly controlled epilepsy. The goal of the study was to determine the serum levels of patients with seizure reduction of at least 50% after addition of LTG, and to assess a possible relationship between the occurrence of adverse effects due to LTG and its serum concentration.
Methods:
Fifteen adult patients were evaluated with respect to seizure reduction. Nine patients had focal seizures with or without generalization, six patients had generalized seizures (Group I). The correlation between the occurrence of adverse effects and LTG serum concentration was calculated in a second group of 63 young adult, and adult patients with epilepsy (Group II).
Results:
The range of the LTG serum concentration in the 15 patients with a 50% or greater reduction of seizure frequency was 1.3-7.1 microg/ml (median = 3.6 microg/ml). In group II patients the serum concentration associated with an adverse effect was not significantly different from the serum concentration in patients without adverse effects. There was, however, a tendency for higher serum concentrations in patients with adverse effects. In the serum concentration range of 5 to 13 microg/ml, the frequency of LTG levels which were accompanied by an adverse effect increased only slowly, whereas above 13-14 microg/ml, there was a steep increase in adverse effects. The serum concentration of four patients with tremor (mean = 14 +/- 2.8 microg/ml) was significantly higher than the LTG level which were in 42 patients who did not have adverse effects at any time (mean = 4.8 +/- 4.1 microg/ml), P = 0.003.
Conclusion:
Our results suggest a target range for LTG serum concentrations of 1-13 microg/ml, especially, if LTG is used as an add on-drug.