Efficacy and safety of domestic Paliperidone extended-release tablets in the treatment of stable schizophrenia / 中国药房

OBJECTIVE To investigate the efficacy and safety of domestic Paliperidone extended-release tablets as a substitute for original Paliperidone extended-release tablets in the treatment of stable schizophrenia. METHODS A total of 65 patients with schizophrenia， who were treated with single original Paliperidone extended-release release tablets for 2 months or more in the outpatient or inpatient department of Shandong Daizhuang Hospital from June 2021 to June 2022， were collected and randomly divided into the domestic group （33 cases） and the original group （32 cases）. The domestic group was treated with the same dose of domestic Paliperidone extended-release tablets instead for 2 months， and the original group continued to use the previous dose of the original drug for 2 months. Positive and negative syndrome scale （PANSS） and treatment emergent symptom scale （TESS） were used to evaluate the two groups at the time of enrollment and the end of 1 week， 1 month and 2 months after enrollment. The incidence of ADR was calculated at the end of 2 months after enrollment. The fasting blood glucose， blood lipid indicators （triglyceride， total cholesterol， low-density lipoprotein， high-density lipoprotein， very-low-density lipoprotein）， serum prolactin levels， and paliperidone blood concentration were determined after the intravenous blood sample was collected. The ratio of paliperidone blood concentration to dose （C/D value） was calculated， and an electrocardiogram was performed. RESULTS There were 31 and 30 patients in the domestic group and the original group who completed the trial， respectively. There were no statistical significances in PANSS score， TESS score or C/D value at the time of enrollment and the end of 1 week， 1 month and 2 months after enrollment； there were no statistical significances in the levels of fasting blood glucose， blood lipid or serum prolactin at the time of enrollment and at the end of 2 months after enrollment （P＞0.05）. PANSS scores of both groups significantly decreased at the end of 1 month and 2 months after enrollment （P＜0.01）. The incidences of ADR were 25.81% in the domestic group and 30.00% in the original group， without significant difference （P＞0.05）， and there were no significant abnormalities in the electrocardiograms of the two groups. CONCLUSIONS Domestic Paliperidone extended-release tablets can directly replace the original tablets in the treatment of stable schizophrenia， and their clinical efficacy and safety are comparable.

Early application of tacrolimus extended-release capsule after kidney transplantation / 器官移植

Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m2) vs. (60±15) mL/(min·1.73 m2), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure.

Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain based on oxycodone hydrochloride extended-release tablet.@*METHODS@#A total of 60 patients with lung cancer pain were randomized into an observation group (30 cases, 1 case dropped off) and a control group (30 cases). In the control group, oxycodone hydrochloride extended-release tablet was given orally, 10 mg a time, once every 12 hours. On the basis of the treatment in the control group, Miao medicinal crossbow acupuncture therapy was applied once every other day in the observation group. The treatment of 14 days was required in the two groups. Before and after treatment, the numerical rating scale (NRS) score, number of break-out pain and Karnofsky performance status (KPS) score were observed in the two groups. The equivalent oxycodone consumption and rate of adverse reactions were recorded, the analgesic effect was evaluated in the two groups.@*RESULTS@#Compared before treatment, the NRS scores and number of break-out pain were decreased while the KPS scores were increased after treatment in the two groups (P<0.01). After treatment, the NRS score and number of break-out pain in the observation group were lower than the control group (P<0.01), the KPS score in the observation group was higher than the control group (P<0.05). The equivalent oxycodone consumption of whole course and the rate of adverse reactions i.e. constipation, drowsiness, nausea and vomiting in the observation group were lower than the control group (P<0.05). The analgesic effect rate was 93.1% (27/29) in the observation group, which was superior to 63.3% (19/30) in the control group (P<0.05).@*CONCLUSION@#On the basis of oxycodone hydrochloride extended-release tablet, Miao medicinal crossbow acupuncture therapy as adjuvant treatment can effectively relieve the pain degree, reduce the number of break-out pain and improve the health status and quality of life in patients with lung cancer pain, enhance the efficacy of medication and reduce its adverse reactions.

Development of metformin HCl granules using brown flaxseed mucilage as a retardant polymer: effects of polymer and drug ratio

Abstract Flaxseed (Linum usitatissimum L.) is the seed of a multipurpose plant of pharmaceutical interest, as its mucilage can be used as a natural matrix to develop extended-release dosage forms and potentially replace synthetic polymers. In this study, a 3² factorial design with two replicates of the central point was applied to optimize the development of extended-release granules of metformin HCl. The total fiber content of the mucilage as well as the friability and dissolution of the formulations were evaluated. The lyophilized mucilage presented a high total fiber content (42.63%), which suggests a high efficiency extraction process. Higher concentrations of the mucilage and metformin HCl yielded less friable granules. In addition, lower concentrations of metformin HCl and higher concentrations of the mucilage resulted in slower drug release during the dissolution assays. The release kinetics for most formulations were better represented by the Hixson-Crowell model, while formulations containing a higher concentration of the mucilage were represented by the Korsmeyer-Peppas model. Nonetheless, five formulations showed a longer release than the reference HPMC formulation. More desirable results were obtained with a higher concentration of the mucilage (13-18%) and a lower concentration of metformin (40%).

Study on pharmacokinetics of osmotic pump tablets of hydrochloride venlafaxine in Chinese healthy volunteers / 中国药理学通报

Aim To evaluate the pharmacokinetics and bioequivalence of two osmotic pump tablets of hydrochloride venlafaxine in Chinese healthy volunteers.Methods The fed test each enrolled twenty-six Chinese healthy volunteers in a randomized-sequence, open-label, two-period crossover single-dose oral test and reference preparations of hydrochloride venlafaxine extended-release tablets.The plasma concentrations of venlafaxine and its active metabolites O-desmethylvenlafaxine were determined by a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method, and the pharmacokinetic parameters and bioequivalence of the two tablets were analyzed using PhoenixTM WinNonlin 6.4 software.Results The pharmacokinetic parameters of venlafaxine after single dose for the test and reference tablets were as follows: Cmax(58.50±19.47)vs(60.14±22.18)μg•L-1, AUC0-t(1 074.1±526.7)vs(1 057.9±539.7)μg•h•L-1, AUC0-∞(1 084.7±536.8)vs(1 067.8±554.0)μ g•h•L-1.The pharmacokinetic parameters of O-desmethylvenlafaxine were as follows: Cmax(101.63±29.64)vs(101.45±31.62)μg•L-1, AUC0-t(2 694.0±834.5)vs(2 702.9±946.4)μg• h•L-1, AUC0-∞(2 753.9±885.5)vs(2 753.2±988.4)μg•h•L-1.The 90% confidence intervals of the geometric mean ratios of Cmax, AUC0-t, AUC0-∞ for the test preparation and the reference preparationwere all within the equivalent interval of 80.00%-125.00%.Conclusion The test and reference preparations of hydrochloride venlafaxine extended-release tablets are bioequivalent in Chinese healthy volunteers under fed conditions.

Effect of methylphenidate hydrochloride combined with mentalization-based family therapy on clinical efficacy and social function in children with attention deficit hyperactivity disorder / 中华行为医学与脑科学杂志

Objective:To observe the effect of methylphenidate hydrochloride (MPH) combined with mentalization-based family therapy (MBFT) on clinical efficacy and social function in children with attention deficit hyperactivity disorder (ADHD).Methods:Sixty-four children with ADHD diagnosed in Wuxi Children's Hospital and Affiliated Hospital of Jiangnan University from June 2019 to May 2021 were selected and divided into observation group ( n=32) and control group ( n=32) according to the random number table.Children in both groups received methylphenidate hydrochloride extended-release tablets, while those in the observation group were given additional MBFT.The duration of treatment was 12 weeks in both groups.The parent symptom questionnaire (PSQ), swanson nolan and pelham-version Ⅳ (SNAP-Ⅳ) parent Al scale, and Weiss impairment functional scale (WFIRS-P) were used to evaluate the effectiveness of treatment.Statistical analysis was performed by SPSS 25.0 statistical software.In particular, the χ2 test was used for counting data and the paired sample t test was used for comparison of measurement data between the two groups before and after treatment. Results:(1) All the PSQ dimension scores of patients in the observation group and the control group after treatment were significantly lower than those before treatment (all P<0.01). Compared with the control group after treatment, the PSQ dimension scores of personality and behavior problems ((1.25±0.15), (0.94±0.18), t=7.484, P<0.001), learning problems ((1.57±0.16), (1.32±0.20), t=5.522, P<0.001), psychosomatic disorders ((0.56±0.11), (0.44±0.13), t=3.986, P<0.001), impulse hyperactivity ((1.76±0.23), (1.54±0.25), t=3.663, P<0.001), anxiety ((0.94±0.12), (0.76±0.11), t=6.255, P<0.001) and hyperactivity index ((1.74±0.19), (1.51±0.16), t=5.238, P<0.001) decreased significantly in the observation group after treatment.(2) Compared with the pre-treatment period, the SNAP-Ⅳ scale scores of attention deficit, impulsivity-hyperactivity and oppositional defiance were significantly lower in both groups after treatment (all P<0.01); and compared with the control group, the SNAP-Ⅳ scale scores of the above three dimensions were significantly lower in the observation group (all P<0.01). (3) All six dimensions (family, learning and school, life skills, self-management, social activities, and risk-taking activities)of the WFIRS-P scale were significantly lower in the children in the observation group after treatment compared with those before treatment (all P<0.01), and all the six dimensions of the WFIRS-P scale were significantly lower in the observation group compared with those in the control group (all P<0.01). Conclusion:Methylphenidate hydrochloride extended-release tablets combined with MBFT can significantly improve the clinical symptoms and social function of children with ADHD.

Progress in technology of long-acting preparations of protein and peptide drugs / 中国药科大学学报

@#As one of the most important biological drugs, protein and peptide drugs have been increasingly used in the prevention, diagnosis and treatment of diseases in recent years. However, most of them need to be injected and lack of long-acting formulations, which brings many troubles to patients suffering from chronic diseases. In this review, we summarized the strategies for engineering long-acting formulations for proteins and peptides via preparation means, including extended-release injection, implant, oral preparations and transdermal drug delivery systems, and analyzed their release mechanisms, research advances, advantages and shortcomings, thereby providing potential approaches for promoting the formulation improvement of these drugs.

Formulation, Development And In Vitro Evaluation Of Tramadol Extended Release Tablets

Objective: The objective of the present study was to develop “once daily” extended release tablets of tramadol (100 mg) by wet granulation using hydrophilic polymer like hydroxy propyl methyl cellulose K100M,K15M and polyethylene oxide (PEO). Methods: The tramadol matrix tablets were prepared by using different polymers like hydroxy propyl methyl cellulose (HPMC K15M and K100M), polyethylene oxide (PEO) as the nontoxic and easily available suitable matrix system. The extended release tablets of tramadol (400 mg) were prepared wet granulation technique. Different pre compression and post compression were performed. In vitro dissolution tests were performed and percentage drug release was calculated. The fourier-transform infrared spectroscopy (FTIR) studies conducted on pure drug tramadol and the optimize formulation (T6). Different release models like zero order, first order, higuchi and Korsemeyer-Peppas were applied to in vitro drug release data in order to evaluate the drug release mechanisms and kinetics. Results: Pre compression and post compression parameters satisfied with pharmacopeia specifications. The In vitro release studies were performed using USP type II apparatus showed that optimized formulation T6 consisting of polyethylene oxide (PEO) with 25 mg of the polymer was found to extended release of tramadol over a period of 24h. The optimized formulation T6 followed the zero order kinetics as correlation coefficient (r2) values are higher than that of first-order release kinetics. In order to understand the complex mechanism of drug release from the optimized formulation T6 matrix system, the in vitro release rate were fitted to Korsemeyer-Peppas model and the release exponent value (n) obtained was 0.82105 exhibited anomalous (non fickian) diffusion mechanism. Conclusion: The present study shows that polyethylene oxide was found to play a great role in controlling release of tramadol from the matrix system. Accordingly it can be concluded that the formulation is robust in the performance is less likely to be affected by the various factors studied.

Effects of Alcohol on Release Characteristics of Metformin Hydrochloride Extended-Release Tablets in Vitro and in Vivo / 中国药学杂志

OBJECTIVE: To investigate the effects of alcohol on release characteristics of metformin hydrochloride extended-release tablets in vitro and in vivo. METHODS: The release behaviors and swelling of self-made metformin hydrochloride extended-release tablets and commercial products Glucophage XR in different release media including water, 5% alcohol, 20% alcohol and 40% alcohol were investigated and similar factor method was used to evaluate the similarity of release. Based on results in vitro, water and the alcoholic medium with significant differences were selected for Beagle dogs experiments to investigate further the effects of alcohol on release characteristics of metformin hydrochloride extended-release tablets in vivo. RESULTS: Along with the increase of the alcohol concentration in the release media, both formation rate of the gel layer became slower and the penetration of the solvents became less in the swelling process, only dissolving a small amount of drug, so the release of self-made tablets and Glucophage XR gradually decreased in vitro. Both release in 40% alcohol produced a significant difference compared with that in water (f2<50), but the release of self-made tablets was greatly similar to Glucophage XR in the same media.In vivo studies of Beagle dogs revealed that an initial low release of both preparations was observed in 40% alcohol which was consistent with the vitro, while a certain increase was observed later, but the overall release was not statistically different from that of the water supply group. Moreover,the main pharmacokinetic parameters of the self-made tablets and Glucophage XR between the water-supply group and the 40% alcohol-supply group had no statistical difference. CONCLUSION: Alcohol has the same effects on the release characteristics of self-made metformin hydrochloride extended-release tablets and Glucophage XR in vitro and in vivo. High concentration of alcohol has a significant effect on the release characteristics in vitro, but it has no significant effect on the overall release in vivo.

Quantitative analysis of 3-isopropylamino-1,2-propanediol as a degradation product of metoprolol in pharmaceutical dosage forms by HILIC-CAD / 药物分析学报

Aryloxypropanolamine is an essential structural scaffold for a variety of β-adrenergic receptor antago-nists such as metoprolol. Molecules with such a structural motif tend to degrade into α, β-hydroxypropanolamine impurities via a radical-initiated oxidation pathway. These impurities are typically polar and nonchromophoric, and are thus often overlooked using traditional reversed phase chromatography and UV detection. In this work, stress testing of metoprolol confirmed the generation of 3-isopropylamino-1,2-propanediol as a degradation product, which is a specified impurity of metoprolol in the European Pharmacopoeia (impurity N). To ensure the safety and quality of metoprolol drug products, hydrophilic interaction chromatography (HILIC) methods using Halo Penta HILIC column (150 mm×4.6 mm, 5 μm) coupled with charged aerosol detection (CAD) were developed and optimized for the separation and quantitation of metoprolol impurity N in metoprolol drug products including metoprolol tartrate injection, metoprolol tartrate tablets, and metoprolol succinate extended-release tablets. These HILIC-CAD methods were validated per USP validation guidelines with respect to speci-ficity, linearity, accuracy, and precision, and have been successfully applied to determine impurity N in metoprolol drug products.

Treatment of Children and Adolescents with Attention Deficit Hyperactivity Disorder and/or Tourette's Disorder with Clonidine Extended Release

We aimed to assess the effectiveness and safety of clonidine extended release (ER) treatment in Korean youth with ADHD and/or Tourette's disorder. We retrospectively reviewed the medical records of 29 children and adolescents treated with clonidine ER. The effectiveness were retrospectively measured at baseline and after 4 and 12 weeks based on the Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scores. Safety was evaluated at each visit based on spontaneous reports from the subjects or from their parents/guardians. Significant decreases in the CGI-S scores for both ADHD (F=23.478, p < 0.001, partial η2=0.540) and tic symptoms (F=15.137, p < 0.001, partial η2=0.443) were noted over 12 weeks. The most common adverse event was somnolence (n=9, 31.0%) and life-threatening adverse effects were not observed. Our results provide preliminary evidence for the effectiveness and safety of clonidine ER.

Influence of genetic polymorphisms in drug metabolism enzymes and transporters on pharmacokinetics of different fluvastatin formulations / 中国药理学与毒理学杂志

OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the pharmacokinetics-genetic polymorphis relationship. METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release (ER) 80 mg tablet and an immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study, ef-fects of BCRP, SLCO1B1, MDR1, CYP2C9, and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using high-performance liquid chromatography-tandem mass spectrometry. RESULTS The SLCO1B1 T521C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1B1 T521C genotype correlated with the AUC0-24of repeat doses (P=0.01). The CYP2C9*3 genotype correlated with the AUC0- 24after the first dose IR 40 mg capsule (P<0.05); however, the difference between CYP2C9*1/*1 and CYP2C9*1/*3 was not statistically significant after repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.

Efficacy and safety of paliperidone extended-release tablets in the treatment of schizophrenia / 中国基层医药

Objective To study the clinical effect and safety of paliperidone extended-release tablets in the treatment of schizophrenia.Methods 80 patients with schizophrenia were selected as the research subjects .Accord-ing to randomized single blind,the patients were divided into two groups ,40 cases in each group.The control group was given risperidone treatment,the observation group used paliperidone extended-release tablets treatment.The total effective rate,positive and negative symptoms score (PANSS score),mental disability score (WHO-DAS score II) and the incidence of adverse reactions were compared between the two groups .Results The clinical total effective rate (95.00%) in the observation group was significantly higher than the control group (80.00%,χ2 =4.114,P <0.05).After treatment, the PANSS score and WHO-DAS II score in the observation group were significantly decreased compared with before treatment (t =8.002,7.761,all P <0.05),which were lower than those in the control group after treatment (t =4.114,3.702,all P <0.05).The incidence rate of adverse reaction between the two groups had no statistically significant difference (7.50% vs.10.00%,χ2 =0.157,P >0.05).Conclusion The clinical efficacy of paliperidone extended-release tablets in the treatment of schizophrenia is significant ,which can effectively relieve patients with mental disorders ,and it is safe and reliable.

LC-MS/MS Method for Quantification of Levetiracetam in Human Plasma and Its Application in Pharmacokinetic Study of Extended-Release Tablets at Fasted And Fed States / 中国药学杂志

OBJECTIVE: To establish an LC-MS/MS method for the determination of levetiracetam to investigate the pharmacokinetics of levetiracetam extended-release tablets at fasted and fed states. METHODS: The separation was achieved on a Waters Symmetry C18 column (3.9 mm×150 mm, 5 μm) with mobile phase consisting of acetonitrile-5 mmol·L-1 ammonium acetate and 0.3% formic acid aqueous solution (10/90, V/V). Two subjects were randomly assigned to receive single oral dose of levetiracetam extended-release tablets 1 000 mg after being fasted and fed by a randomized crossover design. The plasma concentrations of levetiracetam were measured by LC-MS/MS. RESULTS: The calibration curve of levetiracetam in human plasma was linear over the concentration rang of 0.100 0-80.00 μg·mL-1. Under fasted and fed conditions, the main pharmacokinetic parameters of levetiracetam were as follows:ρmax were 20.50 and 19.09 μg·mL-1, AUC0-48 h were 345.4 and 336.3 μg·h·mL-1, tmax were 4.5 and 7.0 h, respectively. CONCLUSION: The method is proved to be convenient, accurate and sensitive, and suitable for the pharmacokinetic study of 1 000 mg levetiracetam extended-release tablets in healthy Chinese volunteers after being fasted and fed. The result suggests that high fat and calories diet has effect on the pharmacokinetics of levetiracetam extended-release tablets, with tmax being delayed.

Application of hypertension prevention knowledge and health education combined with Extended Release Nifedipine Tablets in prevention and treatment of hypertension and its influence on blood pressure control / 中国生化药物杂志

Objective To investigate the application of hypertension prevention knowledge and health education combined with Extended Release Nifedipine Tablets in the prevention and treatment of hypertension and its influence on blood pressure control. Methods 110 cases of hypertension patients in our hospital from March 2015 to April 2016 were randomly divided into two groups, the control group was treated with Extended Release Nifedipine Tablets, and the study group was combined with health education. Results The treatment effect of the study group was significantly better than that of the control group (P<0.05). Conclusion Combined Application of health education is beneficial to improve blood pressure control level in patients with hypertension.

Application of hypertension prevention knowledge and health education combined with Extended Release Nifedipine Tablets in prevention and treatment of hypertension and its influence on blood pressure control / 中国生化药物杂志

Objective To investigate the application of hypertension prevention knowledge and health education combined with Extended Release Nifedipine Tablets in the prevention and treatment of hypertension and its influence on blood pressure control. Methods 110 cases of hypertension patients in our hospital from March 2015 to April 2016 were randomly divided into two groups, the control group was treated with Extended Release Nifedipine Tablets, and the study group was combined with health education. Results The treatment effect of the study group was significantly better than that of the control group (P<0.05). Conclusion Combined Application of health education is beneficial to improve blood pressure control level in patients with hypertension.

Comparative of paliperidone extended release tablets and risperidone tablets for women's glycolipid metabolism of episode schizophrenia / 药物评价研究

Objective To compare the sustained-release tablets paliperidone and risperidone tablets starting glycolipid metabolism in female patients with schizophrenia.Methods Eighty-five cases of women treated in our hospital episode schizophrenia patients were randomly divided into observation group (42 cases) and control group (43 cases).were treated with sustained-release tablets paliperidone and risperidone tablets monotherapy two months.Measuring body mass index before and after treatment (BMI),waist circumference (waist),triglyceride (TG),high density lipoprotein (HDL),fasting plasma glucose (FPG),2 h glucose after OGTT (2 h PG),Positive and Negative Syndrome scale (PANSS) for efficacy evaluation.Results Comparison minutes before treatment PANSS total score and factors,the difference was not statistically significant.After treatment,PANSS total score and factor scores,the difference was not statistically significant.Compared with the previous treatment,both groups PANSS total score and factor scores were significantly decreased after treatment,the difference was statistically significant (P ＜ 0.05).Two groups of patients before treatment indexes,the difference was not statistically significant.After treatment in the control group TG,former TC,HDLC,LDLC,BMI,and waist circumference with treatment,the difference was statistically significant (P ＜ 0.05);the observation group BMI and waist circumference compared with before treatment,the difference was statistically significant (P ＜ 0.05).After observation group TG,TC,LDLC,BMI and waist circumference were significantly lower than the control group,HDLC significantly higher,the difference was statistically significant (P ＜ 0.05).Two FPG,2hPG,SBP and DBP,the difference was not statistically significant (P ＞ 0.05).Adverse reactions in patients in the observation group were significantly lower than the control group,the difference was statistically significant (P ＜ 0.05).Conclusion The sustained-release tablets paliperidone and risperidone female first-episode schizophrenia patients have the same effect,but paliperidone extended release tablets in female patients improve blood lipids,BMI and waist circumference is superior to risperidone.

Optimization of Dosage Regimen of Amoxicillin and Clavulanate Potassium Extended Release Tablets Based on PK/PD Parameters / 中国药师

Objective:To optimize the clinical dosage regimen of amoxicillin and clavulanate potassium extended release ( ER) tablets based on the PK/PD parameters. Methods:Totally 30 healthy subjects ( half male and half female) were randomly divided into three groups, and orally administered the ER tablets respectively under fasting condition, before the meal and after the meal, and the optimal administration time was determined by comparing the pharmacokinetic characteristics. The subjects in the three groups were ad-ministered the ER tablets respectively at low, medium and high dosage, and the optimal dosage and dosing interval were determined based on the PK/PD parameters. Results:Under fasting condition, the AUC of amoxicillin [(32.2 ±15.0) μg·h·ml-1] was sig-nificantly lower than that before the meal [(41.7 ±1.92) μg·h·ml-1] and that after the meal [(42.6 ±17.7) μg·h·ml-1]. In contrast, the AUC of clavulanate acid after the meal [(1.89 ±0.54) μg·h·ml-1] was significantly lower than that under fasting condition [(2.55 ±0.76) μg·h·ml-1] and that before the meal [(2.58 ±0.76) μg·h·ml-1] (P MIC) in 12 h was 5. 5, 7 and 10 h, and the percentage was 46%, 58% and 83%, respectively, and T> MIC in 12 h was 4. 5, 6 and 8 h, and the percentage was 38%, 50% and 67%, re-spectively when MIC was 4. 0μg·ml-1 . Conclusion:It is suggested that amoxicillin and clavulanate potassium ER tablets be taken at the start of a standard meal, 2 tablets per time, twice daily, which is sufficient to achieve T> MIC of 40% -50%.

Pharmacokinetics of atorvastatin and sustained-release metformin fixed-dose combination tablets: two randomized, open-label, 2-way crossover studies in healthy male subjects under fed conditions

Two separate studies were conducted to establish bioequivalence (BE) for two doses of atorvastatin/metformin sustained-release (SR) fixed dose combination (FDC) versus the same dosage of the individual component (IC) tablets in healthy male subjects under fed conditions (study 1, BE of atorvastatin/metformin SR 20/500 mg FDC; study 2, BE of atorvastatin/metformin SR 20/750 mg FDC). Each study was a randomized, open-label, single oral dose, two-way crossover design. Serial blood samples were collected pre-dose and up to 36 hours post-dose for atorvastatin and 24 hours for metformin. Plasma concentrations of atorvastatin, 2-OH atorvastatin and metformin were analyzed using a validated liquid chromatography tandem mass-spectrometry. A non-compartmental analysis was used to calculate pharmacokinetic (PK) variables and analysis of variance was performed on the lognormal-transformed PK variables. A total of 75 subjects completed the study 1 (36 subjects) and study 2 (39 subjects). The 90% confidence intervals for the adjusted geometric mean ratio of Cmax and the AUC0-t were within the predefined 0.80 to 1.25 range. The number of subjects reporting at least one adverse event following FDC treatments was comparable to that following IC treatments. The two treatments were well tolerated. Therefore, atorvastatin/metformin SR 20/500 mg and 20/750 mg FDC tablets are expected to be used as alternatives to IC tablets to decrease the pill burden and increase patient compliance.

Quality control of desvenlafaxine succinate extended-release tablets / 国际药学研究杂志

Objective To establish and validate the assay methods of release, content, content uniformity and related substances of desvenlafaxine succinate (DVS) in extended- release tablets. Methods The ultraviolet spectrophotometric method was used to determine the DVS release from DVS extended-release tablets. The content uniformity, content and related substance were determined by high-performance liquid chromatography (HPLC). To validate all the method, we respectively examined specificity, linearity, recovery rate, precision and stability, etc. Results The results showed that the analysis method for release was specific, the calibration curve was linear in the range of 10-200 µg/ml, and all the recovery, repeatability and intermediate precision met requirements. The method for detection of content and content uniformity was specific and linear in the range of 5-400 µg/ml, the recovery, repeatability and intermediate precision met requirements. The method for related substances was specific and sensitive, the linear and recovery rate met the requirements. All of the solutions were stable during 24 h at room temperature. Conclusion The analysis method for release is simple, sensitive, specific and accurate, the method for content and content uniformity is accurate and reliable, and the method for related substances is specific, sensitive and accurate. These methods are suitable for quality control of DVS extendedrelease tablets.