Pharmacokinetic Interaction of Zonisamide in Rats. Effect of Other Antiepileptics on Zonisamide

• Published in: Journal of Pharmacobio-Dynamics Vol. 15; no. 11; pp. 631 - 639
• Main Authors: KIMURA, Masahiko, TANAKA, Naomi, KIMURA, Yasuhiro, MIYAKE, Katsushi, KITAURA, Teruaki, FUKUCHI, Hiroshi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1992; Pharmaceutical Society of Japan
• Subjects: Administration, Oral; Animals; Anticonvulsants - blood; Anticonvulsants - metabolism; Anticonvulsants - pharmacokinetics; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Blood Proteins - metabolism; Diethylcarbamazine - pharmacology; Drug Interactions; Erythrocytes - metabolism; Half-Life; Isoxazoles - blood; Isoxazoles - metabolism; Isoxazoles - pharmacokinetics; Male; Medical sciences; metabolism; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; Neuropharmacology; Pharmacology. Drug treatments; Phenobarbital - pharmacology; Phenytoin - pharmacology; Rats; Rats, Wistar; Valproic Acid - pharmacology; Zonisamide; Rat; Rodentia; Oral administration; Red blood cell; Anticonvulsant; Metabolism; In vitro; Bound form; Vertebrata; Mammalia; Animal; Distribution; Drug interaction; Mechanism of action; Pharmacokinetics
• ISSN: 0386-846X; 1881-1353
• DOI: 10.1248/bpb1978.15.631

The pharmacokinetics of zonisamide (ZNS) and the effects of phenobarbital (PB), valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) on ZNS kinetics were investigated in rats. The effects of other antiepileptics on the serum protein binding, erythrocyte distribution and metabolism of ZNS were also studied in vitro to elucidate the mechanism of pharmacokinetic interaction of ZNS. ZNS showed a linear disposition kinetics after oral administration of ZNS within the dose examined. Moreover, the pharmacokinetic behaviors of ZNS were not altered after multiple dosing. The decreased t1/2 value of ZNS by PB or CBZ pretreatment and the increased Vd/F value of ZNS by VPA pretreatment were observed, although it showed no marked effect of PHT on ZNS kinetics. The enhanced metabolism of ZNS was observed by PB or CBZ pretreatmtent from an in vitro metabolism study. The serum protein binding and erythrocyte distribution of ZNS showed no significant change in the presence of other antiepileptics in vitro. These results indicate that the decreased t1/2 value of ZNS is attributable to the enzyme inducing effect of PB or CBZ, and that neither protein binding nor erythrocyte distribution of ZNS could be the reason for the increased Vd/F value of ZNS by VPA coadministration.