Flunarizine (flu) is a calcium entry blocker and widely used in the treatment of cerebral and peripheral vascular diseases. It has been also reported to have an anticonvulsant effect. We developed an analytical method of flu serum concentration by high performance liquid chromatography for therapeutic drug monitoring. By using the present method, pharmacokinetic parameters were determined for seven healthy volunteers after a single oral administration and serum concentrations of flu were monitored for seventeen patients with add-on treatment in therapy-resistant epilepsy or cerebrovascular disease. The peak-height ratio of flu to the internal standard (cinnarizine) was linealy related (r=0.9994) to concentrations over the range 5-200ng/ml in the serum. The detective limit was 2 ng/ml in the human serum. The overall average recovery was 99.1±5.1% (n=30). The within-day precision was 3.3% (n=5) and the between-day reproducibility was less than 5% over 5 d. Commonly used antiepileptic agents were found not to interfer in this method. The seven healthy volunteers received a single oral dose 20 mg of flu tablets after overnight fast. The average of the maximal serum concentration and the area under the curve from 0 to 24 h were 55.0±13.4 ng/ml and 552.1±136.1 ng·h/ml, respectively. The elimination from the serum showed a biphasic pattern, with the elimination half-life of 18.8±4.6 h. Flu showed the effect only for the impairment of consciousness in complex partial seizure in two epileptic children, and at this time, the trough concentrations in the serum were 25 and 45 ng/ml.
