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

Kimura, Masahiko; Tanaka, Naomi; Kimura, Yasuhiro; Miyake, Katsushi; Kitaura, Teruaki; Fukuchi, Hiroshi

doi:10.1248/bpb.16.722

Cited by 14 publications

(6 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that ZNS did not sig nificantly modify the ty, values and AUC of VPA and CBZ in rats [18]. In the present study, treatment with ZNS also did not signif icantly affect the ty, and AUC of LTG, sug gesting no effect of ZNS on the LTG pharma cokinetics.…”

Section: Effect O F Cbz On Trough Level O F Repeated Ltg Administrationcontrasting

confidence: 48%

Effects of Various Antiepileptic Drugs on Plasma Levels of Lamotrigine, a Novel Antiepileptic, in Rats

et al. 1997

View full text Add to dashboard Cite

The pharmacokinetics of lamotrigine (LTG) and effects of carbamazepine (CBZ), valproic acid (VPA) and zonisamide (ZNS) on LTG kinetics were investigated in rats. LTG plasma levels were measured by high-performance liquid chromatography (HPLC). A single oral administration of LTG at 2.5–10 mg/kg showed linear disposition kinetics. In the pharmaco-kinetic parameters of LTG when combined with CBZ, the maximal plasma concentration (C_max) and the area under the plasma concentration curve (AUC_0–36) values were significantly lower and the time to maximal plasma concentration (T_max) value was significantly higher than those in LTG alone. Furthermore, the C_max and AUC_0–36 values of LTG when pre-treated with CBZ for 7 days were significantly lower than those from simultaneous treatment with CBZ. The C_max and AUC_0–36 values of LTG when combined with VPA were significantly lower than those for LTG alone. There was no significant difference in the T_max or time of elimination half-life (t_½) values of LTG between simultaneous and pretreatment with VPA. Of the pharmacokinetic parameters of LTG with ZNS combination, the C_max value of LTG after long-term dosings of ZNS decreased significantly, whereas no significant change in C_max was observed after the combined single administration of LTG and ZNS. Single and chronic ZNS treatment did not significantly affect the T_max, t_½ and AUC_0–36 values of LTG. The LTG trough level was significantly reduced by CBZ administration, reached the bottom level at 6 days after starting CBZ administration, and recovered gradually after withdrawal of CBZ. These results suggest that CBZ, VPA and ZNS causes changes in the plasma LTG level. They also suggest that in therapy combining LTG with one of these antiepileptics, especially CBZ, the LTG concentration in plasma should be monitored carefully.

show abstract

Section: Effect O F Cbz On Trough Level O F Repeated Ltg Administrationcontrasting

confidence: 48%

Effects of Various Antiepileptic Drugs on Plasma Levels of Lamotrigine, a Novel Antiepileptic, in Rats

et al. 1997

View full text Add to dashboard Cite

show abstract

“…A study in rats investigating the effect of ZNS on other AEDs indicated that the T,,, and the area under the curve (AUC) values were slightly increased by ZNS coadministration. Overall, however, ZNS had little effect on other AEDs (35). In patients receiving CBZ or PHT as monotherapy, addition of ZNS resulted in a small but significant increase in PHT serum concentrations but not of CBZ concentrations (36).…”

Section: Drug Interactionsmentioning

confidence: 87%

“…In rats, pretreatment with CBZ or phenobarbital (PB) significantly decreased the TI, of ZNS (27). A long-term study evaluating the concentratioddose (CD) ratio of ZNS in patients found that PB, PHT, and CBZ significantly decreased the CD ratio, whereas clonazepam (CZP) and VPA did not (28).…”

Section: Drug Interactionsmentioning

confidence: 99%

Zonisamide

Leppik

1999

Epilepsia

View full text Add to dashboard Cite

Summary: Zonisamide (ZNS) is a broad-spectrum antiepileptic drug in both animal models of epilepsy and patients with epilepsy. It is effective for both localization-related and generalized epilepsies and appears to be particularly potent in progressive myoclonic epilepsy syndromes. Its pharmokinetic profile is favorable, with a long half-life and low protein binding.However, its insolubility may make the development of a parenteral formulation difficult. Its safety profile is good, although teratogenicity in animal models is of concern. Adult doses of 400-600 mg per day in two doses, with blood levels from 20 to 30 mg/ml, appear to be effective.

show abstract

“…Phenobarbital was obtained from Wako Pure Chemical Industries (Osaka, Japan). For intravenous administration, zonisamide was dissolved in a sterile physiological saline containing 40% polyethylene glycol 300 at a concentration of 50 mg/mL as was reported by Kimura et al. (1992a).…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs

Orito

Saito

Fukunaga

et al. 2008

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

The purposes of the present study were to elucidate the pharmacokinetics of zonisamide, determine the presence of a drug interaction with phenobarbital, and evaluate how long any interaction lasted after discontinuation of phenobarbital in dogs. Five dogs received zonisamide (5 mg/kg, p.o. and i.v.) before and during repeated oral administration of phenobarbital (5 mg/kg, bid, for 30-35 days). Zonisamide (5 mg/kg, p.o.) was also administered 8, 10, and 12 weeks after discontinuation of phenobarbital. Blood was sampled until 24 h after each zonisamide administration and serum concentrations of zonisamide were determined. Repeated phenobarbital decreased the maximum serum concentration, area under the serum concentration vs. time curve, apparent elimination half-life, and bioavailability of zonisamide. Total clearance increased. Time to maximum serum concentration and volume distribution were not changed. The maximum serum concentration and area under the serum concentration vs. time curve of zonisamide continued to be low until 10 weeks after the discontinuation of phenobarbital. They were restored to the same serum concentration as before phenobarbital administration 12 weeks after the discontinuation of phenobarbital. These data suggested that repeated administration of a clinical dose of phenobarbital enhanced the clearance of zonisamide and the enhanced clearance lasted at least 10 weeks after the discontinuation of phenobarbital. Caution may be necessary when zonisamide is given with phenobarbital and when antiepileptic therapy is changed from phenobarbital to zonisamide.

show abstract

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

Cited by 14 publications

References 1 publication

Effects of Various Antiepileptic Drugs on Plasma Levels of Lamotrigine, a Novel Antiepileptic, in Rats

Effects of Various Antiepileptic Drugs on Plasma Levels of Lamotrigine, a Novel Antiepileptic, in Rats

Zonisamide

Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs

Contact Info

Product

Resources

About