Zonisamid besitzt in vieler Hinsicht ein günstiges pharmakokinetisches Profil. Das Antikonvulsivum wird rasch resorbiert, hat eine hohe, von der Nahrungsaufnahme unabhängige Bioverfügbarkeit und kann aufgrund der langen Halbwertszeit von etwa 60 Stunden ohne Gefahr nächtlicher Anfälle ein- oder auch zweimal täglich eingenommen werden. Mit anderen, häufig eingesetzten Antikonvulsiva wie Carbamazepin, Phenytoin, Valproat und Lamotrigin führt Zonisamid zu keinen klinisch relevanten Interaktionen, wenngleich Antikonvulsiva, die auf Cyp3A4-Isoenzyme induzierend wirken, den Metabolismus von Zonisamid beeinflussen können.
Abstract
From many points of view zonisamide possesses a favourable pharmacokinetic profile. The anticonvulsive agent is rapidly absorbed, has a high bioavailability independent of the consumption of food and can, on account of its long half-life of about 60 hours, be taken once or also twice a day without the danger of night-time seizures. Zonisamide does not have any clinically relevant interactions with other frequently administered anticonvulsive agents such as carbamazepine, phenytoin, valproate and lamotrigine. However, anticonvulsants that induce the Cyp3A4 isoenzyme may influence the metabolism of zonisamide.
Literatur
1 Fachinformation Zonegran®, Stand März 2007, Eisai Ltd.
2
Siedlik P, Bockbrader H, Chang T. et al .
Effect of food on the oral absorption of zonisamide in normal healthy volunteers.
Pharm Res.
1986;
3
1585
3
Kumagai N, Seki T, Yamada T. et al .
Concentrations of zonisamide in serum, free fraction, mixed saliva and cerebrospinal fluid in epileptic children treated with monotherapy.
J Psychiatry Neurol.
1993;
47
291-292
8 Shah J, Shellenberger K, Canafax D M. Zonisamide: chemistry, biotransformation and pharmacokinetics. In: Levy RH, Mattson RH, Meldrum BS, Perucca E (eds) Antiepileptic Drugs. 5th ed. Philadelphia; Lippincott Williams & Wilkins 2002: 873-879
13 Rosenfeld W E, Bergen D, Garnett W. et al .Steady state drug interaction study of zonisamide and carbamazepine in epileptic patients. American Academy of Neurology 2000
14 Fachinformation Zonegran®, Stand Februar 2007, Eisai Inc.
15
Ojemann L M, Shastri R A, Wilensky A J. et al .
Comparative pharmacokinetics of zonisamide (CI-912) in epileptic patients on carbamazepine or phenytoin monotherapy.
Ther Drug Monit.
1986;
8
293-296
16
Levy R H, Ragueneau-Majlessi I, Brodie M J. et al .
Lack of clinical significant pharmacokinetic interactions between zonisamide and lamotrigine at steady state in patients with epilepsy.
Therapeutic Drug Monitoring.
2005;
27
193-198
17 Brodie M, Wilson E, Smith D. et al .Steady state drug interaction study of zonisamide and lamotrigine in epileptic patients. American Academy of Neurology 2000
19
Schentag J J, Bengo F M, Wilton J H. et al .
Influence of Phenobarbital, cimetidine and renal disease on zonisamide kinetics.
Pharm Res.
1987;
4 (S)
79
20 Shah J. Zonisamide and oral contraceptives: a pharmacokinetic study. Philadelphia; Posterpräsentation bei der Jahrestagung der American Epilepsy Society 2001
21 Mather G G. et al .Drug Interaction. In: Levy RH, Mattson RH, Meldrum BS, Perucca E (eds) Antiepileptic Drugs. 5th ed. Philadelphia; Lippincott Williams & Wilkins 2002: 880-884
22
Griffith S G, Dai Y.
Effect of zonisamide on the pharmacokinetics and pharmacodynamics of a combination ethinyl estradiol-norethindrone oral contraceptive in healthy women.
Clin Ther.
2004;
26
2056-2065
23
Stiff D D, Robicheau J T, Zemaitis M A.
Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative.
Xenobiotica.
1992;
22
1-11
