Aim To investigate the NMR spectroscopy of amlodipine and risperidone.Methods 1D NMR and 2D NMR experimental techniques of gCOSY, gHSQC and gHMBC were wsed. Results Theassignments of the ~1H and ^(13) C NMR data for t...Aim To investigate the NMR spectroscopy of amlodipine and risperidone.Methods 1D NMR and 2D NMR experimental techniques of gCOSY, gHSQC and gHMBC were wsed. Results Theassignments of the ~1H and ^(13) C NMR data for the two drugs were performed and confirmed by theevidence of J_(HF) and J_(CF). Conclusion The structures of amlodipine and risperidone wereconfirmed by careful analysis of regular 1D and 2D NMR spectroscopy.展开更多
Population pharmacokinetic meta-analysis method was used in order to obtain the pharmacokinetic characteristics of risperidone and its active metabolite. Eighteen studies were selected from published papers from 1995 ...Population pharmacokinetic meta-analysis method was used in order to obtain the pharmacokinetic characteristics of risperidone and its active metabolite. Eighteen studies were selected from published papers from 1995 to 2011. A model consisted of two compartments for parent drug and one compartment for its active metabolite combined with a flexible absorption process was developed based on the meta-dataset. The population-predicted apparent clearance for risperidone and 9-hydroxyrisperidone, the active metabolite was 7.66 L/h and 7.38 L/h, and the apparent volume of distribution in the central compartment was 70.6 L and 117 L, respectively. The final model was evaluated by visual predictive check（VPC） based on 1000 times model simulation. This model was adequately used to predict clinical therapeutic drug monitoring（TDM） data from 42 Chinese inpatients. Bias（mean prediction errors, MPE） and precision（root mean squared prediction errors, RMSE） were calculated to statistically analysis the population prediction error. It was demonstrated that the model developed from the meta-dataset was reliable and can be used to facilitate the individualized treatment for a target population.展开更多
In the present study, we investigated the complexation of risperidone with hydroxypropyl-β-cyclodextrin （HP-β-CD） in aqueous solution due to the poor water solubility and low oral bioavailability of risperidone in...In the present study, we investigated the complexation of risperidone with hydroxypropyl-β-cyclodextrin （HP-β-CD） in aqueous solution due to the poor water solubility and low oral bioavailability of risperidone in humans. The effect of temperature on the complexation was examined, and thermodynamic parameters of the complexation process, such as Gibbs free energy change （AG）, enthalpy change （AH） and entropy change （AS）, were also explored. Meantime, the solid dispersion of risperidone with HP-β-CD was prepared and confirmed by Fourier IR spectroscopy and X-ray diffractometry. The experimental results suggested that the complex of the drug with HP-β-CD at a molar ratio of 1：1 could form in aqueous solution, and the complexation was an endothermic and entropy-driven process. The risperidone-HP-β-CD solid dispersion exhibited a remarkable improvement in the dissolution rate of the drug. This might be attributed to the amorphous state, the enhanced wettability as well as the complex formation of the drug with HP-β-CD in aqueous solution.展开更多
Objective To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in pat...Objective To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. Methods The trial was a double-blind, placebo-controlled, parallel- group design. The eligible patients were randomized into 2 treatment groups： sarsasapogenin group （sarsasapogenin plus risperidone for 8 weeks, n = 41） and placebo group （risperidone only for 8 weeks, n = 39）. At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Nega- tive Symptoms Scale （PANSS）, Wechsler Memory Scale （WMS）, modified Chinese Wechsler Adult Intelligence Scale （mWAIS）, Clinical Global Impression （CGI） and Brief Psychiatry Rating Scale （BPRS）. The study period for each subject was 8 weeks and duration of overall trial was 2 years. Results Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. Conclusion Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.展开更多
A new HPLC method has been developed for determining donepezil in human plasma. To find the optimum conditions, a derivatization reaction was performed in different media, and the reaction product was identified by NM...A new HPLC method has been developed for determining donepezil in human plasma. To find the optimum conditions, a derivatization reaction was performed in different media, and the reaction product was identified by NMR and GC-MS after a semi-preparative HPLC separation. Under optimized conditions, donepezil was derivatized by 9-fluorenylmethyl chloroformate in chloroform and carbonate buffer at pH 9.5 in the presence of NaI after solid-phase extraction from a plasma sample. The reaction product was quantified on a reversed-phase TRACER EXCEL ODS-A, 5 μm column using a mixture of acetonitrile–10 mM acetate buffer(pH 6.0)–THF(60:35:5, v/v/v) as the mobile phase with fluorescence detection at 264 nm(ex) and 313 nm(em). Fluoxetine was used as the internal standard. The total run-time of the analysis was about 10 min, and a clean chromatogram was obtained. The developed method was linear over the range of 1–100 ng/mL in 500 μL of plasma samples(r2>0.998). The intra-day and inter-day precision values were in the range of 2.6%–11.6%. The limit of quantification was 1 ng/mL.展开更多
In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidon...In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidone.Schizophrenic patients(six females and seven males)were enrolled in this study.Serial blood samples were collected after drug administration during 63 d,and the drug concentrations were analyzed by LC-MS/MS.Safety and tolerance were evaluated by monitoring the AEs,changes in clinical laboratory results,12-lead ECG,vital signs,physical examination,and injection-site reactions.The extrapyramidal symptoms were evaluated using the ESRS.Efficacy was evaluated by the PANSS and BPRS.Twelve out of the 13 participants completed the trial.There were few clinically meaningful changes in mean clinical laboratory values,vital signs,or ECG parameters,except for the prolactin level and body weight.There were no serious AEs,and those observed were reversible.Significant clinical improvements in PANSS and PANSS-derived BPRS total scores were observed.The mean(standard deviation,coefficient of variation)values for these PK parameters were as follows:C_(max),8.954(8.059,90.0%)ng/mL;area under the curve AUC_(0-t),2453(1156,47.1%)ng·h/mL;AUC_(0-∞),2472(1160,46.9%)ng·h/mL;t_(max),830.0(min:744.0,max:984.0,11.8%)h;and t_(1/2),68.56(10.77,15.7%)h.The PK characteristics of long-acting risperidone showed a high level of inter-individual variation,while there were no clear correlations between PK,efficacy and AEs among the patients in the present study.展开更多
文摘Aim To investigate the NMR spectroscopy of amlodipine and risperidone.Methods 1D NMR and 2D NMR experimental techniques of gCOSY, gHSQC and gHMBC were wsed. Results Theassignments of the ~1H and ^(13) C NMR data for the two drugs were performed and confirmed by theevidence of J_(HF) and J_(CF). Conclusion The structures of amlodipine and risperidone wereconfirmed by careful analysis of regular 1D and 2D NMR spectroscopy.
基金Guangzhou Municipality Medical and Technology Project(Grant No.20131A011087)Beijing Key Lab of Diagnostics and Therapeutics for Psychiatric disorders 2013 Open Foundation(Grant No.2013JSJB01)Beijing Municipal Education Commission Science and Technology Development Program(Grant No.KM201110025025)
文摘Population pharmacokinetic meta-analysis method was used in order to obtain the pharmacokinetic characteristics of risperidone and its active metabolite. Eighteen studies were selected from published papers from 1995 to 2011. A model consisted of two compartments for parent drug and one compartment for its active metabolite combined with a flexible absorption process was developed based on the meta-dataset. The population-predicted apparent clearance for risperidone and 9-hydroxyrisperidone, the active metabolite was 7.66 L/h and 7.38 L/h, and the apparent volume of distribution in the central compartment was 70.6 L and 117 L, respectively. The final model was evaluated by visual predictive check（VPC） based on 1000 times model simulation. This model was adequately used to predict clinical therapeutic drug monitoring（TDM） data from 42 Chinese inpatients. Bias（mean prediction errors, MPE） and precision（root mean squared prediction errors, RMSE） were calculated to statistically analysis the population prediction error. It was demonstrated that the model developed from the meta-dataset was reliable and can be used to facilitate the individualized treatment for a target population.
基金Science and Technology Million Project of Inner Mongolia Medical University(Grant No.YKD2014KJBW012)
文摘In the present study, we investigated the complexation of risperidone with hydroxypropyl-β-cyclodextrin （HP-β-CD） in aqueous solution due to the poor water solubility and low oral bioavailability of risperidone in humans. The effect of temperature on the complexation was examined, and thermodynamic parameters of the complexation process, such as Gibbs free energy change （AG）, enthalpy change （AH） and entropy change （AS）, were also explored. Meantime, the solid dispersion of risperidone with HP-β-CD was prepared and confirmed by Fourier IR spectroscopy and X-ray diffractometry. The experimental results suggested that the complex of the drug with HP-β-CD at a molar ratio of 1：1 could form in aqueous solution, and the complexation was an endothermic and entropy-driven process. The risperidone-HP-β-CD solid dispersion exhibited a remarkable improvement in the dissolution rate of the drug. This might be attributed to the amorphous state, the enhanced wettability as well as the complex formation of the drug with HP-β-CD in aqueous solution.
基金supported by thegrant of Stanley Medical Research Institute(No.02I-005),USA
文摘Objective To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. Methods The trial was a double-blind, placebo-controlled, parallel- group design. The eligible patients were randomized into 2 treatment groups： sarsasapogenin group （sarsasapogenin plus risperidone for 8 weeks, n = 41） and placebo group （risperidone only for 8 weeks, n = 39）. At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Nega- tive Symptoms Scale （PANSS）, Wechsler Memory Scale （WMS）, modified Chinese Wechsler Adult Intelligence Scale （mWAIS）, Clinical Global Impression （CGI） and Brief Psychiatry Rating Scale （BPRS）. The study period for each subject was 8 weeks and duration of overall trial was 2 years. Results Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. Conclusion Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.
文摘A new HPLC method has been developed for determining donepezil in human plasma. To find the optimum conditions, a derivatization reaction was performed in different media, and the reaction product was identified by NMR and GC-MS after a semi-preparative HPLC separation. Under optimized conditions, donepezil was derivatized by 9-fluorenylmethyl chloroformate in chloroform and carbonate buffer at pH 9.5 in the presence of NaI after solid-phase extraction from a plasma sample. The reaction product was quantified on a reversed-phase TRACER EXCEL ODS-A, 5 μm column using a mixture of acetonitrile–10 mM acetate buffer(pH 6.0)–THF(60:35:5, v/v/v) as the mobile phase with fluorescence detection at 264 nm(ex) and 313 nm(em). Fluoxetine was used as the internal standard. The total run-time of the analysis was about 10 min, and a clean chromatogram was obtained. The developed method was linear over the range of 1–100 ng/mL in 500 μL of plasma samples(r2>0.998). The intra-day and inter-day precision values were in the range of 2.6%–11.6%. The limit of quantification was 1 ng/mL.
基金Foundation items:The National Major Scientific and Technological Special Project for"Significant New Drug Development"during the Twelfth Five-year Planning Period of China(Grant No.2014ZX09303303).
文摘In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidone.Schizophrenic patients(six females and seven males)were enrolled in this study.Serial blood samples were collected after drug administration during 63 d,and the drug concentrations were analyzed by LC-MS/MS.Safety and tolerance were evaluated by monitoring the AEs,changes in clinical laboratory results,12-lead ECG,vital signs,physical examination,and injection-site reactions.The extrapyramidal symptoms were evaluated using the ESRS.Efficacy was evaluated by the PANSS and BPRS.Twelve out of the 13 participants completed the trial.There were few clinically meaningful changes in mean clinical laboratory values,vital signs,or ECG parameters,except for the prolactin level and body weight.There were no serious AEs,and those observed were reversible.Significant clinical improvements in PANSS and PANSS-derived BPRS total scores were observed.The mean(standard deviation,coefficient of variation)values for these PK parameters were as follows:C_(max),8.954(8.059,90.0%)ng/mL;area under the curve AUC_(0-t),2453(1156,47.1%)ng·h/mL;AUC_(0-∞),2472(1160,46.9%)ng·h/mL;t_(max),830.0(min:744.0,max:984.0,11.8%)h;and t_(1/2),68.56(10.77,15.7%)h.The PK characteristics of long-acting risperidone showed a high level of inter-individual variation,while there were no clear correlations between PK,efficacy and AEs among the patients in the present study.
