Coadministration of vigabatrin and valproate in children with refractory epilepsy.
The effects of adding vigabatrin (GVG) to the antiepileptic regimens of 16 children with refractory epilepsy have been studied. One-half of the regimens included sodium valproate (VPA). Parameters studied were seizure reduction, platelet GABA-T activity, and steady-state plasma concentrations (CSS) of GVG and VPA. Add-on GVG reduced the seizure frequency both in patients receiving VPA (from 42.9 to 4.5 seizures/month, p < 0.01) and in those without VPA (from 60.0 to 31.7 seizures/month, p < 0.05). GVG also reduced GABA-T activity in both groups (from 19.4 to 5.4, p < 0.001 and from 8.3 to 4.5 pmol/min/mg of protein, p < 0.05, respectively). Seizure reduction and GABA-T inhibition were greater in patients taking VPA than in those who were not. In patients receiving VPA, no significant changes were observed in VPA CSS values before and after the addition of GVG. On the other hand, no differences were found in GVG CSS values between patients with and without VPA. It is concluded that the coadministration of GVG to valproate reduces the frequency of seizures in refractory epileptic children and does not affect the steady-state plasma concentrations of either drug. Therefore, their association could be useful in clinical practice.
Armijo
J A
JA
Clinical Pharmacology Service, M. de Valdecilla University Hospital, University of Cantabria School of Medicine, Santander, Spain.
Arteaga
R
R
Valdizán
E M
EM
Herranz
J L
JL
D000612:4-Aminobutyrate Transaminase / Q000097:blood; D000293:Adolescent; D000614:Aminocaproates / Q000008:administration & dosage* / Q000097:blood; D000927:Anticonvulsants / Q000008:administration & dosage*; D001792:Blood Platelets / Q000201:enzymology; D002648:Child; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D016037:Single-Blind Method; D014635:Valproic Acid / Q000008:administration & dosage* / Q000097:blood; D020888:Vigabatrin
D000614:Aminocaproates; D000927:Anticonvulsants; D014635:Valproic Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin