PMID- 17617289
OWN - NLM
STAT- MEDLINE
DCOM- 20070807
LR  - 20141120
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 29
IP  - 4
DP  - 2007 Apr
TI  - Relative bioavailability of tizanidine 4-mg capsule and tablet formulations after 
      a standardized high-fat meal: a single-dose, randomized, open-label, crossover 
      study in healthy subjects.
PG  - 661-9
AB  - BACKGROUND: An immediate-release, multiparticulate capsule formulation of 
      tizanidine has been developed to modify tizanidine pharmacokinetic 
      characteristics in an attempt to decrease adverse events (AEs) while maintaining 
      effectiveness in the management of spasticity. OBJECTIVE: This study was designed 
      to compare the pharmacokinetic properties and tolerability of a single dose (4 
      mg) of an immediate-release, multiparticulate tizanidine capsule versus a 
      commercially available tablet (reference) administered after a standardized 
      high-fat meal. METHODS: This single-dose, randomized, open-label, 2-way crossover 
      study in healthy, nonsmoking adult subjects was conducted at MDS Pharma Services, 
      Belfast, United Kingdom. Subjects were randomly assigned to receive the 
      capsule-tablet or tablet-capsule treatment. The 2 treatment periods were 
      separated by a 6-day washout period. All treatments were administered after a 
      standardized high-fat meal. To determine plasma tizanidine pharmacokinetic 
      properties, blood samples were collected over 24 hours after administration. The 
      predetermined bioequivalence range for the test drug (capsule) was 80% to 125% of 
      the reference drug (tablet). Drug tolerability was assessed using routine 
      physical examination, including vital-sign measurements; laboratory analysis 
      (hematology, biochemistry, and urinalysis); 12-lead electrocardiography; direct 
      observation; spontaneous reporting; and non specific questioning. RESULTS: This 
      study included 18 subjects (12 men, 6 women; mean [SD] age, 26 [7] years). The 
      mean height and body weight of the subjects were 176 (8) cm and 70.1 (9.6) kg, 
      respectively. The peak exposure, as measured by mean natural 
      logarithm-transformed C(max) values, was significantly lower with the capsule 
      compared with the tablet (2.7 vs 4.0 ng/mL; P < 0.019), and mean TmaX was 
      significantly longer (2.6 vs 1.2 hours; P < 0.001). The 90% CIs for the 
      capsule:tablet treatment ratios were 70.55 to 121.94 for AUC(0-lat) and 70.12 to 
      118.75 for AUC(0-infinity). The capsule did not achieve the protocol-defined 
      definition of bioequivalence when given after a high-fat meal. All AEs were 
      transient and mild in intensity, with asthenia being the most common event with 
      the capsule and tablet formulations, occurring in 5 (28%) and 8 (44%) subjects, 
      respectively. CONCLUSIONS: In this small study in healthy volunteers, after a 
      single oral dose was administered following a high-fat meal, the mean C(max) was 
      significantly lower and mean T(max) was significantly longer with the capsule 
      formulation of tizanidine compared with the tablet. The capsule formulation was 
      found not to be bioequivalent to the tablet when given with food. Based on these 
      findings, caution is needed when a patient is switched between the capsule and 
      tablet formulations of tizanidine, or when the timing of administration of either 
      formulation is changed in relation to food ingestion.
FAU - Henney, Herbert R 3rd
AU  - Henney HR 3rd
AD  - Acorda Therapeutics, Inc., Hawthorne, New York 10532, USA. hhenney@acorda.com
FAU - Shah, Jaymin
AU  - Shah J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Capsules)
RN  - 0 (Dietary Fats)
RN  - 0 (Dosage Forms)
RN  - 0 (Muscle Relaxants, Central)
RN  - 0 (Tablets)
RN  - 6AI06C00GW (tizanidine)
RN  - MN3L5RMN02 (Clonidine)
SB  - IM
MH  - Adult
MH  - Asthenia/chemically induced
MH  - Biological Availability
MH  - Capsules
MH  - Clonidine/administration & dosage/adverse effects/*analogs & 
      derivatives/blood/pharmacokinetics
MH  - Cross-Over Studies
MH  - *Dietary Fats
MH  - Dosage Forms
MH  - Female
MH  - Food-Drug Interactions
MH  - Humans
MH  - Male
MH  - Muscle Relaxants, Central/*administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Tablets
EDAT- 2007/07/10 09:00
MHDA- 2007/08/08 09:00
CRDT- 2007/07/10 09:00
PHST- 2007/01/24 00:00 [accepted]
PHST- 2007/07/10 09:00 [pubmed]
PHST- 2007/08/08 09:00 [medline]
PHST- 2007/07/10 09:00 [entrez]
AID - S0149-2918(07)00112-9 [pii]
AID - 10.1016/j.clinthera.2007.04.012 [doi]
PST - ppublish
SO  - Clin Ther. 2007 Apr;29(4):661-9. doi: 10.1016/j.clinthera.2007.04.012.