OBJECTIVE To investigate the bioequivalence of risperidone tablets in healthy volunteers.METHODS 2 mg reference or test tablets were given to 22 healthy male volunteers in a randomized two-way crossover design.The concentrations of risperidone and 9-hydroxy-risperidone were determined by HPLC/MS.The bioequivalence of two formulations were investigated by the analysis of variance,two one side t-test and 90% confidence interval test.RESULTS The pharmacokinetic parameters of risperidone reference and test tablets were as follows:AUC0-t(124.80±116.22) and(137.19±118.12) μg·h·L-1,ρmax(17.00±6.87) and(19.24±7.63) μg·L-1,tmax(1.52±0.93) and(1.32±0.58) h,Ke(0.19±0.13) and(0.18±0.12) h-1,t1/2Ke(7.58±8.72) and(6.31±4.65) h.The pharmacokinitic parameters of 9-hydroxy-risperidone were as follows:AUC0-t(564.3±182.42) and(580.01±205.38) μg·h·L-1,ρmax(20.00±9.84) and(20.05±10.38) μg·L-1,tmax(5.93±3.59) and(5.70±3.18) h,Ke(0.032±0.007 8) and(0.034±0.008 0) h-1,t1/2Ke(23.15±6.07) and(21.50±4.62) h.The pharmacokinitic parameters of total active moiety were as follows:AUC0-t(692.54±235.57) and(720.80±260.22) μg·h·L-1,ρmax(32.00±9.42) and(33.89±13.02) μg·L-1,tmax(2.27±1.50) and(1.98±1.25) h,Ke(0.033±0.008 6) and(0.035±0.007 8) h-1,t1/2Ke(22.72±6.94) and(20.98±4.34) h,respectively.The mean relative bioavailability of tested vs reference tablets were(113.4±25.85)%,(104.6±20.83)%,(105.4±19.64)% for risperidone,9-hydroxy-risperidone and total active moiety respectively.CONCLUSION The two formulations are bioequivalent.
JIO Zheng;YU Yun-qiu;ZHNG Li;LI Zhong-dong;SHI Xio-jin;ZHONG Ming-kng.
Study on Bioequivalence of Risperidone Tablets [J]. Chinese Pharmaceutical Journal, 2006, 41(05): 384-387
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参考文献
[1] HE H，RIHARDSON J S. A pharmacological，pharmacokinetic and clinical overview of risperidone，a new antipsychotic that blocks serotonin 5-HT2 and dopamine D2 receptors[J] . Int Clin Psychopharmacol，1995，10(1)：19-30.
[2] BALANT-GORGIA A E，GEX-FABRORY M，GENET C，et al. Therapeutic drug monitoring of risperidone using a new，rapid HPLC method： reappraisal of interindividual variability factors[J] . Ther Drug Monit，1999，21 (1)：105-115.
[3] XIAO H，YANG J，ZHANG S N，et al. Determination of risperidone and its metabolite in human plasma by high performance liquid chromatography[J] . Chin J Chromatogr(色谱)，1999，17(4)：395-397.
[4] REMMERIE B M，SIPS L L，DE VRIES R，et al. Validated method for the determination of risperidone and 9-hydroxyrisperidone in human plasma by liquid chromatography-tandem mass spectrometry[J] . J Chromatogr B Analyt Technol Biomed Life Sci，2003，783(2)：461-472.
[5] GUTIERREZ R，LEE P I，HUANG M L，et al. Risperidone： effects of formulations on oral bioavailability[J] . Pharmacotherapy，1997，17(3)：599-605.
[6] ROH H K，KIM C E，CHUNG W G，et al. Risperidone metabolism in relation to CYP2D6*10 allele in korean schizophrenic patients[J] . Eur J Clin Pharmacol，2001，57(9)：671-675.
[7] MIHARA K，KONDO T，YASUI-FURUKORI N，et al. Effects of various CYP2D6 genotypes on the steady-state plasma concentrations of risperidone and its active metabolite，9-hydroxyrisperidone，in Japanese patients with schizophrenia[J] . Ther Drug Monit，2003，25(3)：287-293.
