PMID- 22595151
OWN - NLM
STAT- MEDLINE
DCOM- 20121011
LR  - 20131121
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 34
IP  - 6
DP  - 2012 Jun
TI  - Comparative fasting bioavailability of dispersible and conventional tablets of 
      risperidone: a single-dose, randomized-sequence, open-label, two-period crossover 
      study in healthy male Chinese volunteers.
PG  - 1432-9
LID - 10.1016/j.clinthera.2012.04.027 [doi]
AB  - BACKGROUND: Risperidone (RIS), an atypical antipsychotic drug, is used for the 
      treatment of psychoses associated with schizophrenia and other psychiatric 
      disorders in adult and pediatric populations. An oral dispersible tablet 
      formulation of risperidone has been developed. This study was conducted to 
      provide support for marketing authorization of this drug in China. OBJECTIVE: 
      This study was designed to compare the pharmacokinetic (PK) properties and 
      bioavailability of 2 RIS formulations-the dispersible formulation (test) and a 
      branded formulation (reference) in healthy male Chinese volunteers. METHODS: This 
      single-dose, randomized-sequence, open-label, 2-period crossover study involved 
      22 healthy male Chinese volunteers. Equal numbers of eligible participants were 
      randomly assigned to receive either the test drug (2 mg) or the same dose of the 
      reference formulation, followed by a 2-week washout period and administration of 
      the alternate formulation. The study drugs were administered after a 10-hour 
      overnight fast. Blood samples were collected before dosing and at 0.33, 0.67, 1, 
      1.5, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72, and 96 hours after dosing. 
      Plasma concentrations of RIS and its active metabolite, 9-hydroxyrisperidone 
      (9-OH-RIS), were measured using LC-MS/MS. The safety profile was evaluated by 
      recording adverse events (AEs), assessed using physical examination including 
      vital signs, spontaneous reporting, and clinical laboratory results. The 2 
      formulations were considered to have met the requirements for bioequivalence if 
      the 90% CIs for the log-transformed C(max) and AUC values were within the 
      predetermined ranges of 75% to 133% and 80% to 125%, respectively, according to 
      the guidelines of the State Food and Drug Administration (SFDA) of China. 
      RESULTS: All 22 volunteers (mean [SD] age, 22.2 [1.98] years; weight, 64.07 
      [5.93] kg; height, 173 [5] cm; and body mass index, 21.2 [1.67] kg/m(2)) that 
      were enrolled completed the study. For RIS, the 90% CIs for the ratios of C(max), 
      AUC(0-t), and AUC(0-infinity) were 93.2% to 116.7%, 97.9% to 111.3%, and 98.0% to 
      111.6%, respectively. For 9-OH-RIS, the 90% CIs were 95.8% to 113.9%, 100.2% to 
      109.7%, and 100.5% to 110.3%, respectively. All values were within the 
      predetermined bioequivalence range. Seven AEs were reported somnolence (4 
      subjects [9.1%]) and dizziness (3 subjects [6.8%]). All AEs were transient and 
      considered mild by physicians. CONCLUSIONS: The test (dispersible) and reference 
      tablets met the regulatory criteria for bioequivalence as defined by the SFDA. 
      Both formulations were well tolerated. Chinese Clinical Trials registration 
      number: ChiCTR-TRC-12001996.
CI  - Copyright (c) 2012 Elsevier HS Journals, Inc. All rights reserved.
FAU - Huang, Mingzhu
AU  - Huang M
AD  - Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and 
      Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Shen-Tu, Jianzhong
AU  - Shen-Tu J
FAU - Hu, Xingjiang
AU  - Hu X
FAU - Chen, Junchun
AU  - Chen J
FAU - Liu, Jian
AU  - Liu J
FAU - Wu, Lihua
AU  - Wu L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120516
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Tablets)
RN  - L6UH7ZF8HC (Risperidone)
SB  - IM
MH  - Antipsychotic Agents/administration & dosage/adverse effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Cross-Over Studies
MH  - Humans
MH  - Male
MH  - Risperidone/administration & dosage/adverse effects/*pharmacokinetics
MH  - Spectrometry, Mass, Electrospray Ionization
MH  - Tablets
EDAT- 2012/05/19 06:00
MHDA- 2012/10/12 06:00
CRDT- 2012/05/19 06:00
PHST- 2012/01/30 00:00 [received]
PHST- 2012/04/25 00:00 [revised]
PHST- 2012/04/25 00:00 [accepted]
PHST- 2012/05/19 06:00 [entrez]
PHST- 2012/05/19 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
AID - S0149-2918(12)00291-3 [pii]
AID - 10.1016/j.clinthera.2012.04.027 [doi]
PST - ppublish
SO  - Clin Ther. 2012 Jun;34(6):1432-9. doi: 10.1016/j.clinthera.2012.04.027. Epub 2012 
      May 16.