Influence of oral adsorbent AST-120 on anticonvulsive effect of zonisamide in rats.
The influence of oral adsorbent AST-120 (Kremezin) on the anticonvulsive effect and pharmacokinetics of zonisamide was investigated. Oral administration of zonisamide (50 mg/kg) blocked the appearance of the tonic extension induced by maximal electroshock seizure. This effect of zonisamide was inhibited by the oral coadministration of AST-120 (5 g/kg). In pharmacokinetics study, the serum zonisamide concentration after coadministration of zonisamide and AST-120 was significantly lower than that of single administration of zonisamide. However, the anticonvulsive effect of zonisamide was not affected by the administration of AST-120 1.5 h after zonisamide administration. In this condition, the serum zonisamide concentration was not changed. In the in vitro study, AST-120 completely adsorbed zonisamide. These findings suggest that when AST-120 is administered concurrently with zonisamide, a significant inhibition of the anticonvulsive effect of zonisamide occurs, and the decrease in serum zonisamide concentration by the adsorption effect of AST-120 is related to this phenomenon.
Toyota
T
T
Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama 700-8558, Japan.
Kitamura
Y
Y
Araki
H
H
Sadakane
N
N
Futagami
K
K
Furuno
K
K
Gomita
Y
Y
D000284:Administration, Oral; D000327:Adsorption / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D002244:Carbon / Q000008:administration & dosage*; D004347:Drug Interactions / Q000502:physiology; D004597:Electroshock; D007555:Isoxazoles / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010087:Oxides / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D010087:Oxides; D000078305:Zonisamide; D002244:Carbon; C040896:AST 120