[Therapeutic ranges of anti-epileptic drugs in monotherapy of children].
Relationship between steady-state plasma concentrations of phenobarbitone (PB), phenytoin (PHT), primidone (PRM), carbamazepine (CBZ) and sodium valproate (VPA) and their efficacy and toxicity, were studied in 392 pediatric outpatients, long-term treated in monotherapy for epileptic seizures or febrile convulsions, in order to establish "target" values which may be used, as reference, in clinical practice. The concentration-efficacy and toxicity curves suggest target values of 20, 15, 9, 10, 6 and 70 mg/l for PB, PB derived from PRM, PRM, PHT, CBZ and VPA respectively. Above 25 mg/l of PB, 20 of PHT and 100 of VPA, markedly decreased the probability of response in refractory patients, and a clear increase in toxicity was shown. Above 7 mg/l of CBZ a decrease in the percentage of seizure-free patients was observed, without an increase of toxicity. For PRM no efficacy "ceiling" was found but side effects increased. The target values proposed may be helpful as a reference for the initial dosage of antiepileptic drugs in children, during monotherapy. Nevertheless, final doses should be adjusted according to clinical response of each patient.
Armijo Simón
J A
JA
Servicio de Farmacología Clínica, Hospital Universitario M. de Valdecilla, Facultad de Medicina, Universidad de Cantabria, Santander.
Herranz Fernández
J L
JL
Valiente Domingo
R
R
Arteaga Manjón-Cabeza
R
R
D000927:Anticonvulsants / Q000008:administration & dosage / Q000145:classification / Q000627:therapeutic use*; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D012640:Seizures / Q000188:drug therapy
D000927:Anticonvulsants