Zonisamide: its pharmacology, efficacy and safety in clinical trials

Acta Neurologica Scandinavica

Volumn 126, Issue S194, 2012, Pages 19-28

  Brodie, M J ^a   Ben Menachem, E ^b   Chouette, I ^c   Giorgi, L ^c  

^a WESTERN INFIRMARY   (United Kingdom)

^b UNIVERSITY OF GOTHENBURG   (Sweden)

^c EISAI CO LTD   (Japan)

Author keywords

Antiepileptic drug; Clinical trial; Efficacy; Epilepsy; Pharmacokinetics; Pharmacology; Tolerability; Zonisamide

Indexed keywords

CARBAMAZEPINE; LAMOTRIGINE; PHENOBARBITAL; PHENYTOIN; PLACEBO; VALPROIC ACID; ZONISAMIDE; ANTICONVULSIVE AGENT; ISOXAZOLE DERIVATIVE;

AGITATION; ANOREXIA; AREA UNDER THE CURVE; CONCENTRATION LOSS; DIPLOPIA; DIZZINESS; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FOCAL EPILEPSY; HEADACHE; HUMAN; IRRITABILITY; MAXIMUM PLASMA CONCENTRATION; MONOTHERAPY; NAUSEA; NONHUMAN; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; SOMNOLENCE; TREATMENT DURATION; WEIGHT REDUCTION; ANIMAL; CHEMISTRY; CLINICAL TRIAL (TOPIC); DOSE RESPONSE; EPILEPSY; TREATMENT OUTCOME;

ANIMALS; ANTICONVULSANTS; CLINICAL TRIALS AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; EPILEPSY; HUMANS; ISOXAZOLES; TREATMENT OUTCOME;

EID: 84868097093     PISSN: 00016314     EISSN: 16000404     Source Type: Journal    
DOI: 10.1111/ane.12016     Document Type: Review

References (60)

1. Uno H, Kurokawa M, Natsuka K et al. Studies on substituted 1, 2-benzisoxazole derivatives. Chem Pharm Bull (Tokyo) 1976;24:632-43.
2. Uno H, Kurokawa M, Masuda Y, Nishimura H. Studies on 3-substituted 1, 2-benzisoxazole derivatives. 6. Syntheses of 3-(sulfamoylmethyl)-1, 2-benzisoxazole derivatives and their anticonvulsant activities. J Med Chem 1979;22:180-3.
3. Masuda Y, Karasawa T, Shiraishi Y, Hori M, Yoshida K, Shimizu M. 3-Sulfamoylmethyl-1, 2-benzisoxazole, a new type of anticonvulsant drug. Pharmacological profile. Arzneimittelforschung 1980;30:477-83.
4. ® Summary of Product Characteristics. 2012; http://www.medicines.org.uk/emc/medicine/16240/SPC/Zonegran%20capsules (accessed 9 August 2012).
5. ® Prescribing Information. 2012; http://us.eisai.com/package_inserts/Zonegran_PI.pdf (accessed 9 August 2012).
6. Schauf CL. Zonisamide enhances slow sodium inactivation in Myxicola. Brain Res 1987;413:185-8.
7. Rock DM, Macdonald RL, Taylor CP. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res 1989;3:138-43.
8. Suzuki S, Kawakami K, Nishimura S et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res 1992;12:21-7.
9. Kito M, Maehara M, Watanabe K. Mechanisms of T-type calcium channel blockade by zonisamide. Seizure 1996;5:115-9.
10. Okada M, Kaneko S, Hirano T et al. Effects of zonisamide on extracellular levels of monoamine and its metabolite, and on Ca2 + dependent dopamine release. Epilepsy Res 1992;13:113-9.
11. Kaneko S, Okada M, Hirano T, Kondo T, Otani K, Fukushima Y. Carbamazepine and zonisamide increase extracellular dopamine and serotonin levels in vivo, and carbamazepine does not antagonize adenosine effect in vitro: mechanisms of blockade of seizure spread. Jpn J Psychiatry Neurol 1993;47:371-3.
12. Mizuno K, Okada M, Kaneko S et al. Effects of zonisamide, carbamazepine and valproate on monoamine metabolism in rat striatum and hippocampus. Jpn J Psychiatry Neurol 1994;48:406-8.
13. Okada M, Kaneko S, Hirano T et al. Effects of zonisamide on dopaminergic system. Epilepsy Res 1995;22:193-205.
14. Mizuno K. Effects of carbamazepine and zonisamide on acetylcholine levels in rat striatum. Nihon Shinkei Seishin Yakurigaku Zasshi 1997;17:17-23.
15. Okada M, Hirano T, Kawata Y et al. Biphasic effects of zonisamide on serotonergic system in rat hippocampus. Epilepsy Res 1999;34:187-97.
16. Masuda Y, Karasawa T. Inhibitory effect of zonisamide on human carbonic anhydrase in vitro. Arzneimittelforschung 1993;43:416-8.
17. Masuda Y, Noguchi H, Karasawa T. Evidence against a significant implication of carbonic anhydrase inhibitory activity of zonisamide in its anticonvulsive effects. Arzneimittelforschung 1994;44:267-9.
18. Biton V. Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol 2007;30:230-40.
19. Mimaki T, Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H. Interaction of zonisamide with benzodiazepine and GABA receptors in rat brain. Med J Osaka Univ 1990;39:13-7.
20. Ueda Y, Doi T, Tokumaru J, Willmore LJ. Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures. Brain Res Mol Brain Res 2003;116:1-6.
21. Okada M, Kawata Y, Mizuno K, Wada K, Kondo T, Kaneko S. Interaction between Ca2 + , K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode. Br J Pharmacol 1998;124:1277-85.
22. Macdonald RL. Zonisamide: mechanisms of action. In: Levy RH, Matton RH, Meldrum BS, Perucca E, eds. Antiepileptic drugs, 5th edn. Philadelphia: Lippincott, Williams & Wilkins Healthcare, 2002;867-72.
23. Kakegawa N. An experimental study on the modes of appearance and disappearance of suppressive effect of antiepileptic drugs on kindled seizure. Psychiatr Neurol Jpn 1986;88:81-98.
24. Hamada K, Song HK, Ishida S, Yagi K, Seino M. Contrasting effects of zonisamide and acetazolamide on amygdaloid kindling in rats. Epilepsia 2001;42:1379-86.
25. Kamei C, Oka M, Masuda Y, Yoshida K, Shimizu M. Effects of 3-sulfamoylmethyl-1, 2-benzisoxazole (AD-810) and some antiepileptics on the kindled seizures in the neocortex, hippocampus and amygdala in rats. Arch Int Pharmacodyn Ther 1981;249:164-76.
26. Wada Y, Hasegawa H, Okuda H, Yamaguchi N. Anticonvulsant effects of zonisamide and phenytoin on seizure activity of the feline visual cortex. Brain Dev 1990;12:206-10.
27. Bartoszyk GD, Hamer M. The genetic animal model of reflex epilepsy in the Mongolian gerbil: differential efficacy of new anticonvulsive drugs and prototype antiepileptics. Pharmacol Res Commun 1987;19:429-40.
28. Nakamura J, Tamura S, Kanda T et al. Inhibition by topiramate of seizures in spontaneously epileptic rats and DBA/2 mice. Eur J Pharmacol 1994;254:83-9.
29. Ito T, Hori M, Masuda Y, Yoshida K, Shimizu M. 3-Sulfamoylmethyl-1, 2-benzisoxazole, a new type of anticonvulsant drug. Electroencephalographic profile. Arzneimittelforschung 1980;30:603-9.
30. Ito T, Hori M, Kadokawa T. Effects of zonisamide (AD-810) on tungstic acid gel-induced thalamic generalized seizures and conjugated estrogen-induced cortical spike-wave discharges in cats. Epilepsia 1986;27:367-74.
31. Takano K, Tanaka T, Fujita T, Nakai H, Yonemasu Y. Zonisamide: electrophysiological and metabolic changes in kainic acid-induced limbic seizures in rats. Epilepsia 1995;36:644-8.
32. Schulze-Bonhage A. Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother 2010;11:115-26.
33. Kochak GM, Page JG, Buchanan RA, Peters R, Padgett CS. Steady-state pharmacokinetics of zonisamide, an antiepileptic agent for treatment of refractory complex partial seizures. J Clin Pharmacol 1998;38:166-71.
34. Shah J, Shellenberger K, Canafax DM. Zonisamide. Chemistry, biotransformation, and pharmacokinetics. In: Levy RH, Mattson RH, Meldrum BS, Perucca E, eds. Antiepileptic drugs, 5th edn. Philadelphia: Lippincott, Williams & Wilkins, 2002;873-9.
35. Sills G, Brodie M. Pharmacokinetics and drug interactions with zonisamide. Epilepsia 2007;48:435-41.
36. Matsumoto K, Miyazaki H, Fujii T, Amejima H, Furukawa H, Hashimoto M. Binding of sulfonamides to erythrocyte proteins and possible drug-drug interaction. Chem Pharm Bull (Tokyo) 1989;37:2807-10.
37. Ragueneau-Majlessi I, Levy RH, Bergen D et al. Carbamazepine pharmacokinetics are not affected by zonisamide: in vitro mechanistic study and in vivo clinical study in epileptic patients. Epilepsy Res 2004;62:1-11.
38. Levy RH, Ragueneau-Majlessi I, Brodie MJ, Smith DF, Shah J, Pan WJ. Lack of clinically significant pharmacokinetic interactions between zonisamide and lamotrigine at steady state in patients with epilepsy. Ther Drug Monit 2005;27:193-8.
39. Levy RH, Ragueneau-Majlessi I, Garnett WR et al. Lack of a clinically significant effect of zonisamide on phenytoin steady-state pharmacokinetics in patients with epilepsy. J Clin Pharmacol 2004;44:1230-4.
40. Ragueneau-Majlessi I, Levy RH, Brodie M, Smith D, Shah J, Grundy JS. Lack of pharmacokinetic interactions between steady-state zonisamide and valproic acid in patients with epilepsy. Clin Pharmacokinet 2005;44:517-23.
41. Ojemann LM, Shastri RA, Wilensky AJ et al. Comparative pharmacokinetics of zonisamide (CI-912) in epileptic patients on carbamazepine or phenytoin monotherapy. Ther Drug Monit 1986;8:293-6.
42. Mather GG, Shah J. Zonisamide. Drug interactions. In: Levy RH, Mattson RH, Meldrum BS, Perucca E, eds. Antiepileptic drugs, 5th edn. Philadelphia: Lippincott, Williams & Wilkins, 2002;880-4.
43. Griffith SG, Dai Y. Effect of zonisamide on the pharmacokinetics and pharmacodynamics of a combination ethinyl estradiol-norethindrone oral contraceptive in healthy women. Clin Ther 2004;26:2056-65.
44. Schmidt D, Jacob R, Loiseau P et al. Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial. Epilepsy Res 1993;15:67-73.
45. Faught E, Ayala R, Montouris GG; Zonisamide 922 Trial Group. Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures. Neurology 2001;57:1774-9.
46. Sackellares JC, Ramsay RE, Wilder BJ, Browne TR III, Shellenberger MK. Randomized, controlled clinical trial of zonisamide as adjunctive treatment for refractory partial seizures. Epilepsia 2004;45:610-7.
47. Brodie MJ, Duncan R, Vespignani H, Solyom A, Bitenskyy V, Lucas C. Dose-dependent safety and efficacy of zonisamide: a randomized, double-blind, placebo-controlled study in patients with refractory partial seizures. Epilepsia 2005;46:31-41.
48. Chadwick DW, Marson AG. Zonisamide add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev 2005;4:CD001416.
49. Mayer T, Silver G, Remy C, Lemesle-Martin M, Hirsch E. Efficacy and safety of zonisamide as an adjunctive therapy for partial epilepsy uncontrolled with one antiepileptic drug. J Neurol 2005;252(Suppl 2):79-80, [abstract].
50. Mayer T, Silver G, Remy C, Lemesle-Martin M, Hirsch E. Efficacy and safety of zonisamide as an adjunctive therapy for partial epilepsy uncontrolled with one antiepileptic drug. Poster presented at the 15th Annual Meeting of the European Neurological Society, Vienna, Austria; 20 June 2005 (poster number 291).
51. Lu Y, Xiao Z, Yu W et al. Efficacy and safety of adjunctive zonisamide in adult patients with refractory partial-onset epilepsy: a randomized, double-blind, placebo-controlled trial. Clin Drug Investig 2011;31:221-9.
52. Baulac M, Brodie MJ, Patten A, Segieth J, Giorgi L. Efficacy and tolerability of zonisamide versus controlled-release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomized, double-blind, non-inferiority trial. Lancet Neurol 2012;11:579-88.
53. Glauser T, Ben-Menachem E, Bourgeois B et al. ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2006;47:1094-120.
54. Wroe SJ, Yeates AB, Marshall A. Long-term safety and efficacy of zonisamide in patients with refractory partial-onset epilepsy. Acta Neurol Scand 2008;118:87-93.
55. Brodie MJ. Zonisamide as adjunctive therapy for refractory partial seizures. Epilepsy Res 2006;68(Suppl 2):S11-6.
56. Chung S, Wang N, Hank N. Comparative retention rates and long-term tolerability of new antiepileptic drugs. Seizure 2007;16:296-304.
57. Catarino CB, Bartolini E, Bell GS, Yuen AW, Duncan JS, Sander JW. The long-term retention of zonisamide in a large cohort of people with epilepsy at a tertiary referral centre. Epilepsy Res 2011;96:39-44.
58. Ben-Menachem E. Weight issues for people with epilepsy - a review. Epilepsia 2007;48(Suppl 9):42-5.
59. Biton V. Effect of antiepileptic drugs on bodyweight: overview and clinical implications for the treatment of epilepsy. CNS Drugs 2003;17:781-91.
60. Wellmer J, Wellmer S, Bauer J. The impact of zonisamide on weight. A clinical study in 103 patients with epilepsy. Acta Neurol Scand 2009;119:233-8.