Once daily monotherapy with prolonged-release valproate minitablets given in the evening--a chronopharmacological study.
Chronopharmacological investigations concerning efficacy, side effects and circadian serum concentration are lacking for many antiepileptic drugs. In this study 27 patients with focal or generalized epilepsy receiving a single dosage of prolonged-release valproate given in the evening were included. The valproate serum concentration over a course of 24 hours and their correlation with the value measured at 9:00 am was examined. In approximately 60% of the patients the serum level measured at 9:00 am corresponded to the peak value. In an additional 33% of the patients the peak value was reached at either 12:00 midnight or at 3:00 am. During the course of the day all patients showed on average an additional decline in these values compared to the 9:00 am serum level of 41%. In only a third of the patients did the 24-hour profile exhibit an average increase that exceeded the 9:00 am value by as much as 4%. In the case of the 24-hour serum profile, when the daily dosage was weight-correlated no values for the normal dosage range (18 - 24 mg/kg body weight) gave values that exceeded or fell below the so-called therapeutic serum level range (50 - 100 mg/l). Neither seizures nor new adverse reactions occurred in this group. Therefore, in the case of adults and young adults, therapy with valproate prolonged-release at a dose rate of 24 mg/kg preparation given as a single dosage in the evening will be sufficient for seizure control in most patients. The low-dosage group (10 - 17 mg/kg body weight) exhibited values that fell below this range in the afternoon and early evening. The results are discussed with regards to the treatment in young adults and the elderly.