Therapeutic Monitoring of Antiepileptic Drugs: A Comparison Between a Czech and a Swedish University Hospital

Abstract

Plasma concentrations obtained during routine therapeutic monitoring of antiepileptic drugs (AED) (N03A ATC group) were compared in patients treated with one or several AED in the University Hospitals in Ostrava, Czech Republic and Huddinge, Sweden. Request and reply forms for therapeutic drug monitoring (TDM) were used as a source of mean plasma concentrations (PC). The study included 2,824 adult out- and inpatients in Huddinge treated from 1995 to 1999 and 1,268 outpatients treated in Ostrava from 1993 to 2004. PC of valproic acid in Huddinge and all AED except clonazepam in Ostrava were analyzed with gas-liquid chromatography. Plasma concentrations of clonazepam in Ostrava and all AED except valproic acid in Huddinge were analyzed by HPLC. The differences in PC were tested by Student's t-test. Chi(2) method was used for the differences in the distribution of PC relative to the therapeutic window. The mean plasma concentrations generally reached the apparent therapeutic ranges but were below the range in the cases of phenytoin monotherapy in both hospitals, and clonazepam, phenobarbital and phenytoin in polytherapy in Ostrava. In monotherapy 33% of the analyses showed sub-therapeutic concentrations in Huddinge, compared to 38% in Ostrava. Eight percent of the analyses showed potentially toxic concentrations in Huddinge, but only 3% in Ostrava. The highest number of sub-therapeutic concentrations was detected for phenytoin in both hospitals: 59% in Huddinge, 78% in Ostrava. In polytherapy only slight differences between the hospitals were found. PC/dose ratios were significantly lower in polytherapy than in monotherapy for carbamazepine and valproic acid in both hospitals. In contrast a higher PC/dose ratio was found in polytherapy for phenytoin in both cohorts and for lamotrigine in Ostrava. Drug treatment of epilepsy in our two hospitals is surprisingly similar in terms of achieved plasma concentrations, in spite of socioeconomic and cultural differences between our two countries. This may be explained by the long experience with TDM in both hospitals, which has the inherent capacity to promote evidence based drug therapy.