PMID- 19695391
OWN - NLM
STAT- MEDLINE
DCOM- 20091027
LR  - 20181201
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 31
IP  - 6
DP  - 2009 Jun
TI  - Bioequivalence of zonisamide orally dispersible tablet and immediate-release 
      capsule formulations: results from two open-label, randomized-sequence, 
      single-dose, two-period, two-treatment crossover studies in healthy male 
      volunteers.
PG  - 1244-55
LID - 10.1016/j.clinthera.2009.06.012 [doi]
AB  - BACKGROUND: To make it easier for patients who are prescribed zonisamide to 
      administer their medicine, a rapidly disintegrating oral tablet formulation has 
      been developed. OBJECTIVE: These 2 trials assessed the bioequiva-lence of a new 
      orally dispersible tablet formulation of zonisamide (test) versus an 
      immediate-release reference capsule. METHODS: Study 1 assessed the bioequivalence 
      of a 100-mg orally dispersible tablet versus a 100-mg reference capsule. Study 2 
      assessed the bioequivalence of a 300-mg test tablet versus three 100-mg reference 
      capsules. Both trials were open-label, randomized-sequence, single-dose, 
      2-period, 2-treatment crossover studies in consenting healthy male volunteers 
      aged 18 to 55 years. A 4-week washout separated treatment periods. The zonisamide 
      test tablet was placed on the tongue and, after it had dispersed in saliva, 
      swallowed without water. Zonisamide serum concentrations were analyzed using a 
      validated high-performance liquid chromatography assay with tandem mass 
      spectrome-try detection (lower limit of quantification, 10 ng/nL). Bioequivalence 
      was concluded if the 90% CI of the ratio of AUC(0-72) and C(max) were within the 
      regulatory criteria of 0.80 to 1.25. The safety profile was assessed through 
      adverse events (AEs) and analysis of laboratory and echocardiogram parameters. 
      RESULTS: In study one, 36 male subjects were enrolled and randomized (mean [SD] 
      age, 26.1 [6.9] years; weight, 77.6 [11.0] kg; race: white, 35 [97.2%], and 
      Asian, 1 [2.8%]). Of those, 7 were withdrawn prior to completion (5 were lost to 
      follow-up, 1 failed the drug screening, 1 withdrew due to AEs, and 1 was excluded 
      due to undisclosed medical history). In study two, 40 male subjects were enrolled 
      and randomized (mean [SD] age, 31.2 [10.3] years; weight, 76.1 [9.0] kg; race: 
      white, 38 [95.0%], black, 1 [2.5%], and other, 1 [2.5%]). Of those, 2 were 
      withdrawn prior to completion (1 failed the urine drug screening and 1 withdrew 
      consent). The ratios (90% CIs) of AUC(0-72) for the 100-mg and 300-mg test 
      formulations were 1.00 (0.98-1.02) and 1.00 (0.98-1.01), respectively. The ratios 
      (90% CIs) of C(max) were 0.97 (0.94-1.00) and 0.98 (0.95-1.00). A total of 25 
      subjects experienced treatment-emergent AEs in study 1; of these, 8 events in 3 
      patients were considered to be possibly or probably related to study drug 
      administration. A total of 21 subjects experienced treatment-emergent AEs in 
      study 2; of these, 11 events in 6 subjects were considered to be possibly or 
      probably related to study drug administration. All AEs and laboratory and ECG 
      findings were similar between formulations. CONCLUSIONS: The test formulation of 
      zonisamide met regulatory criteria for bioequivalence to the reference 
      formulation in these healthy male volunteers. Both formulations were generally 
      well tolerated at both dose levels.
FAU - Maanen, Rob van
AU  - Maanen Rv
AD  - Eisai Limited, Hatfield, United Kingdom. Rob_vanmaanenweisai.net
FAU - Bentley, Darren
AU  - Bentley D
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anticonvulsants)
RN  - 0 (Capsules)
RN  - 0 (Isoxazoles)
RN  - 0 (Tablets)
RN  - 459384H98V (Zonisamide)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Anticonvulsants/administration & dosage/adverse effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Capsules
MH  - Chromatography, High Pressure Liquid
MH  - Cross-Over Studies
MH  - Electrocardiography
MH  - Follow-Up Studies
MH  - Humans
MH  - Isoxazoles/administration & dosage/adverse effects/*pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Tablets
MH  - Tandem Mass Spectrometry
MH  - Therapeutic Equivalency
MH  - Zonisamide
EDAT- 2009/08/22 09:00
MHDA- 2009/10/29 06:00
CRDT- 2009/08/22 09:00
PHST- 2009/04/23 00:00 [accepted]
PHST- 2009/08/22 09:00 [entrez]
PHST- 2009/08/22 09:00 [pubmed]
PHST- 2009/10/29 06:00 [medline]
AID - S0149-2918(09)00195-7 [pii]
AID - 10.1016/j.clinthera.2009.06.012 [doi]
PST - ppublish
SO  - Clin Ther. 2009 Jun;31(6):1244-55. doi: 10.1016/j.clinthera.2009.06.012.