Toxicology and kinetics of long-term intraventricular infusion of phenytoin and valproic acid in pigs: experimental study.
The effect of continuous intraventricular infusion of phenytoin and valproic acid into the brain of pigs was studied through quantitative measurement of animal behavior, pathological study of animal's brain and measurement of the levels of these drugs in the blood and C.S.F. Two groups of five animals each were treated with increasingly doses of the drugs until the apparition of toxic effects and the dead of animals. Normal behavior was observed with doses up to 3 mg/day of phenytoin and 1.5 mg/day of valproic acid. Toxic effects consisted on severe unsteadiness and muscular rigidity. Pathological study of the brains revealed that there were no damage attributable to the intraventricular infusion of the drugs. The present study suggests that intrathecal or intraventricular infusion of phenytoin and valproic acid could be well tolerated by humans and it leads us to consider subsequent clinical studies in epileptic patients.
Martínez
R
R
Department of Neurosurgery, Púerta de Hierro Clinic, Autonomous University of Madrid, Spain.
Vaquero
J
J
De La Morena
L V
LV
Tendillo
F
F
Aragonés
P
P
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008134:Long-Term Care; D010672:Phenytoin / Q000493:pharmacokinetics / Q000633:toxicity*; D013552:Swine; D014635:Valproic Acid / Q000493:pharmacokinetics / Q000633:toxicity*
D014635:Valproic Acid; D010672:Phenytoin