Once daily monotherapy with prolonged-release valproate minitablets given in the evening--a chronopharmacological study.
BACKGROUND
Chronopharmacological investigations concerning efficacy, side effects and circadian serum concentration are lacking for many antiepileptic drugs.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Graf
W
W
Department of Neurology - Epilepsy Center, University Erlangen-Nürnberg, Erlangen, Germany.
Fraunberger
B
B
Yang
T
T
Kerling
F
F
Pauli
E
E
Stefan
H
H
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D002909:Chronobiology Phenomena; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D055870:Drug Chronotherapy; D004827:Epilepsy / Q000188:drug therapy*; D004829:Epilepsy, Generalized / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013607:Tablets; D014635:Valproic Acid / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D013607:Tablets; D014635:Valproic Acid