Effect of aminophylline upon the protective activity of common antiepileptic drugs and their plasma levels in mice.
Aminophylline (50 mg/kg) decreased the protective efficacy of carbamazepine (20 mg/kg), diphenylhydantoin (8-12 mg/kg), phenobarbital (20 and 25 mg/kg), and valproate (250 and 300 mg/kg) against electroconvulsions in mice. On the other hand, aminophylline (5 mg/kg) was devoid of such activity. Plasma levels of antiepileptic drugs were measured with the help of the Abbott TDx analyzer and after administration of carbamazepine (20 mg/kg), diphenylhydantoin (10 mg/kg), phenobarbital (25 mg/kg), and valproate (250 mg/kg) were as follows: 8.61, 6.48, 24.3 and 329 micrograms/ml, respectively. Aminophylline (50 mg/kg) remained without any significant influence upon these plasma levels. This may lead to the conclusion that aminophylline-induced reversal of antiepileptic drug activity is not dependent upon a pharmacokinetic mechanism and probably occurs at the neuronal level.
Czuczwar
S J
SJ
Department of Pharmacology, Medical School, Lublin, Poland.
Janusz
W
W
Szczepanik
B
B
Wamil
A
A
Kleinrok
Z
Z
D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002220:Carbamazepine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010672:Phenytoin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism
D000927:Anticonvulsants; D000628:Aminophylline; D002220:Carbamazepine; D010672:Phenytoin; D010634:Phenobarbital