Risperidone Tablets Research Articles

Effect of a decoction of Lophira alata (Banks ex P. Gaertn) on the pharmacokinetics of risperidone: Study of a drug-herb interaction

Drug interactions may cause a drug to be more or less effective (synergism or antagonism), or cause unexpected effects on the body. Risperidone is a second-generation atypical antipsychotic medication while Lophira alata is a plant used traditionally to treat psychotic disorders. A large number of patients with psychosis have been reported to simultaneously use both orthodox and traditional medicines in Africa. This research was carried out to determine the effect of concomitant administration of risperidone and Lophira alata in healthy human volunteers. The first phase of the research was carried out to establish the baseline pharmacokinetic profile of risperidone 2 mg in 18 male subjects. The second phase was carried out after a 2-week washout period, where the subjects were randomly divided into three equal groups and group A received risperidone 2 mg and decoction of the herb (9.4mg/kg) concurrently, group B received risperidone 2 mg and decoction of the herb (9.4mg/kg) was administered after 1 hour and group C received a decoction of the herb (9.4mg/kg) and risperidone 2 mg was administered after 1 hour. Blood samples were collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours after drug administration, and plasma analyses were carried out using a developed RP-HPLC method to determine the plasma concentrations. Subsequently, Kinetica 5.0 software was used to extrapolate pharmacokinetic parameters from the plasma concentrations. Results show that there was a significant (p < 0.05) increase in the rate of absorption (ka), peak plasma concentration (Cmax) and measure of drug exposed to the body (AUC0-∞) but significant (p < 0.05) decrease in the time to achieve peak plasma concentration (tmax), half-life of absorption (t1/2a) and extent of drug distribution (Vd) when risperidone and Lophira alata were administered concurrently. Drug-herb interaction was observed to be more significant (p < 0.05), when Lophira alata was administered concurrently with risperidone than when administered one hour before or after Lophira alata. Decoction of Lophira alata interacts with risperidone tablets when administered together, which may be attributed to alteration in the mechanism of risperidone absorption by Lophira alata.

Psychiatric assistance in the hospitalization of adolescents with chronic diseases

Hospitalization is an unpleasant experience for all patients, likewise for adolescent patients. The most common stressors experienced by adolescents undergoing hospitalization include loss of freedom, control, and privacy; fear of injury to the body or changes in self-image; fear of disability, pain, and death; as well as separation with peers, home, and school. The stressor can trigger mental and behavioral disorders, so it can ultimately affect the therapy process and outcome. The role of psychiatrists in adolescent hospitalization is to assist, detect mental disorders that may occur, and provide appropriate procedures to overcome the disorder and prevent worsening of symptoms. This case report describes a 17-year-old teenage girl patient who was consulted to the psychiatry department because she looked sad. Patient experienced long periods of hospitalization, including having been cared in isolation and intensive care room, and had invasive procedures as well. The patient was diagnosed with a Major Depressive Episode without Psychotic Symptoms. Pharmacological therapy with 0.5 mg Risperidone tablet every 24 h orally (evening), while the non-pharmacological therapy given was supportive psychotherapy and psychoeducation to the parent.

Psychological and Behavioral Factors Associated with Cyclic Vomiting Syndrome: Case Report

Introduction:Cyclic vomiting syndrome is a disorder of unknown etiology and pathogenesis characterized by recurrent and stereotypical vomiting episodes with varying intervals from baseline or normal health in between. The biopsychosocial model proposes that disease does not result from a single etiology but from systems that interact simultaneously at the cellular, tissue, organismal, interpersonal, and environmental levels. In addition, psychosocial factors have direct and reverse physiological and pathological consequences. Case: In this case report, A 17-year-old boy was consulted to the psychiatry department because of repeated vomiting suspected of psychological factors. The patient was hospitalized due to vomiting. This vomiting has been experienced by the patient since around 2 months before the examination. Patient’s father and stepmother actually really love this patient, but in the patient's perception, the patient's father and mother are less adequate in how to show their affection. The patient realized that his father loved him but felt in some ways, the patient was uncomfortable because he felt that he did not fit his father's mindset. Conclusion:The patient was diagnosed with Psychological and Behavioral Factors Associated with Cyclic Vomiting Syndrome (F54). Pharmacological therapy with 12.5 mg Amytriptiline tablet, 0.5 mg Risperidone tablet, and 5 mg Clobazam tablet every 24 hours orally (evening), while the non-pharmacological therapy given was supportive psychotherapy and psychoeducation to the parent.

Letter to the Editor: Rethinking The Cost Of Antipsychotic Treatment: The Average Cost Of The Drugs Used In Turkey In 2020.

Letter to the Editor: Rethinking The Cost Of Antipsychotic Treatment: The Average Cost Of The Drugs Used In Turkey In 2020.

6.22 The Combination of Kampo and Western Antipsychotic Drugs Were Effective for 20 Cases in Child Psychiatric Outpatients

Kampo is the Japanese herbal traditional medicine formula, with a root from ancient China, that is used for irritation, mood swing, and agitation in Japan. Ninety percent of Japanese doctors have an experience of prescribing Kampo, and 80% of doctors have combined Kampo and a Western antipsychotic drug (WAD). The indication of atypical WAD is for the irritability and agitation with autism spectrum disorder (ASD), and Kampo is used for peripheral symptoms in the child and adolescent psychiatric patient. For now, risperidone and aripiprazole are the only choices under the Japanese health insurance system to treat children with ASD. This retrospective case series report was conducted in 20 children who received Kampo and a WAD, from April 1, 2017 to December 31, 2020, at our child and adolescent psychiatric outpatient clinic. Their ages ranged from 7 to 19 years. Their age, gender, IQ test (Wechsler Intelligence Scale for Children–Fourth Edition [WISC-4], Tanaka-Binet-5 test, Kyoto Scale of Psychological Development), the severity that DSM-5 defines on the initial examination and the end of this research (none = Level 0, mild = Level 1, moderate = Level 2, severe = Level 3), dropouts, side effects, and the number of medications were surveyed. The average age was 12.2 years (7-19). The ratio of males to females was 19:1. The average IQ was 69.4 (22-143). There were no side effects from Kampo. Seven children had a blood test, and their average serum potassium level was 4.0 mEq/l (3.5-4.4). In addition, 0.5 (25%) of them had any type of drug and food allergies, 6 (30%) had febrile convulsion, abnormality of EEG, and epilepsy, and 3 (15%) had any severe physical disabilities. The initial diagnosis (maximum 2) was 11 (55%) with pervasive developmental disorder and ASD, 9 (45%) with ADHD, 2 (10%) with ODD, 12 (60%) with intellectual disability containing below average IQ (BAIQ), 14 (70%) had continued combined medicine, 5 (25%) had dropped out of the child and adolescent psychiatric outpatient clinic, 6 (30%) had taken multiple WADs. The average Kampo dose per day was 4.6 g (1 package is 2.5 g). The average administration duration was 14.4 month (2-41). The price of a risperidone tablet (2 mg) is $0.40 USD, aripiprazole (3 mg) is $0.60 USD, and Kampo is $0.34 to $0.16 USD per 1 package. The average severity level according to the DSM-5 on the initial examination was 1.95 (1-3). The average severity at the end of this research was 1.17 (0-3). The combination of Kampo and WADs might alleviate the severity of children in the child and adolescent psychiatric outpatient.

Genotyping as a Key Element of Sample Size Optimization in Bioequivalence of Risperidone Tablets.

Risperidone is a derivative of benzisoxazole and is widely used for schizophrenia and other psychiatric illnesses in both adults and children. Previous studies have confirmed that it is a highly variable drug (within-subject variability ≥30%). To reduce the large sample size required for bioequivalence researches on highly variable drugs, a role for genotyping in the design of the bioequivalence study was employed. A randomized, open-label, two-period crossover study was adopted: 20 subjects with specific genotypes carrying cytochrome P450 (CYP)2D6*10 were randomized to two groups to receive a single oral dose of trial formulation or reference formulation with a 2-week washout period. Blood concentrations of risperidone (parent drug) and 9-hydroxy risperidone (active metabolite) were measured by high-performance liquid chromatography-tandem mass spectrometry. Eighteen out of the 20 subjects completed the study (two did not finish the test in the second period). The pharmacokinetic parameters of AUClast, AUC∞ and Cmax for the 18 subjects after a single oral dose of the trial or reference preparation were 216.1±88.7 and 220.5±96.8ng·h/mL; 221.6±93.1 and 226.4±103.5ng·h/mL; 36.7±10.3 and 36.0±10.2ng/mL, respectively. The CVw of risperidone in natural logarithm-transformed Cmax was 22.4 and 25.38% for 9-hydroxy risperidone. The test formulation met the Food and Drug Administration guidelines and regulation criteria for bioequivalence. By controlling the genotype, it could actually help reduce the CVw, which may be a feasible method to decrease the sample size for the bioequivalence study of highly variable drugs.

Synthesis and Characterization of Impurities Listed in United States Pharmacopeia of Risperidone Tablets

Synthesis and Characterization of Impurities Listed in United States Pharmacopeia of Risperidone Tablets

Comparative study of the efficacy and safety between blonanserin and risperidone for the treatment of schizophrenia in Chinese patients: A double-blind, parallel-group multicenter randomized trial

This randomized, double-blind study compared the efficacy and safety of blonanserin and risperidone to treat Chinese schizophrenia patients aged ≥18 and < 65 years. Patients with Positive and Negative Syndrome Scale (PANSS) total scores ≥70 and ≤ 120 were randomized to receive blonanserin or risperidone using a gradual dose-titration method (blonanserin tablets: 8–24 mg/day; risperidone tablets: 2–6 mg/day), twice daily. Treatment populations consisted of 128 blonanserin-treated patients and 133 risperidone-treated patients. Intention-to-treat analysis was performed using the last observation carried forward method. Reductions of PANSS total scores by blonanserin and risperidone treatment were −30.59 and −33.56, respectively. Risperidone treatment was associated with elevated levels of serum prolactin (67.16% risperidone versus 52.31% blonanserin) and cardiac-related abnormalities (22.39% risperidone versus 12.31% blonanserin), and blonanserin patients were more prone to extrapyramidal side effects (48.46% blonanserin versus 29.10% risperidone). In conclusion, blonanserin was as effective as risperidone for the treatment of Chinese patients with schizophrenia. The overall safety profiles of these drugs are comparable, although blonanserin was associated with a higher incidence of EPS and risperidone was associated with a higher incidence of prolactin elevation and weight gain. Thus, blonanserin is useful for the treatment of Chinese schizophrenia patients.

Do users of risperidone who switch brands because of generic reference pricing fare better or worse than non-switchers? A New Zealand natural experiment.

This study evaluated patient health outcomes and any impact on healthcare costs consequent to the implementation of generic reference-pricing of risperidone in New Zealand using national datasets. Reference pricing risperidone reduced the price of the originator brand by 50 % as well as overall expenditure on risperidone tablets. Half of all patients made a single switch to generic risperidone, with the remainder making multiple switches between brands. 1.5 % made a switch-back to the originator brand. No difference was found in use of healthcare services between switchers and non-switchers of the originator brand or versus the comparator group. This refutes the available literature on brand-to-generic and generic-to-generic switching.

Association study of IL-10 gene promoter polymorphisms and efficacy of risperidone treatment of schizophrenic patients with first episode

Objective To investigate association of IL-10 gene promoter polymorphisms with first episode schizophrenic and efficacy of risperidone. Methods 513 schizophrenic patients with first episode(patient group) and 627 health controls(control group)participated in this study. Genotyping for IL-10 gene label single nucleotide polymorphism(SNP)sites-592A/C (rs1800872), -1082A/G(rs1800896), -819T/C(rs1800871) were performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)genotyping technology.513 patients were administered orally risperidone for 8 weeks.Clinical efficacy were evaluated with PANSS. Results The frequences of rs1800896 genotypes (332: 166: 15, 453: 161: 13; χ2=7.55, df=2, P=0.02) and alleles(830: 196, 1067: 187; χ2 =7.09, df=1, P=0.008, OR=1.35, 95%CI=1.08~1.68) showed significant differences between patient group and control group, however only allele differences showed statistical significance after Bonferroni correction(P=0.024). The frequencies of rs1800872and rs1800871 genotypes and alleles had no significant differences between patient group and control group(P>0.05). There were no significant differences of haplotype frequences between patient group and control group(P>0.05). There were no significant differences of genotypes (134: 209: 38, 61: 59: 12; χ2=5.16, df=2, P=0.08; 244: 129: 8, 88: 37: 7; χ2=4.57, df=2, P=0.10; 188: 158: 35, 54: 64: 14; χ2 =2.80, df=2, P=0.25)and alleles (477: 285, 181: 83; χ2=3.03, df=1, P=0.08; 617: 145, 213: 51; χ2 =0.01, df=1, P=0.92; 534: 228, 172: 92; χ2=2.22, df=1, P=0.14) frequences of rs1800872, rs1800896, rs1800871 between effective group(381cases) and invalid group(132 cases) of Risperidone efficacy(P>0.05), while ATC haplotype frequences had significant difference between two groups(χ2=7.501, P=0.006, OR(95%CI)=2.420(1.262-4.640)). Conclusion IL-10 gene rs1800896 polymorphism may be associated with susceptibility to schizophrenia.The clinical curative effect of risperidone in the treatment of schizophrenia is associated with ATC haplotype, ATC haplotype may be good predictors to the overall curative effect of risperidone. Key words: First episode schizophrenia; Gene polymorphisms; Interleukin 10; Risperidone tablets

Interactions between active pharmaceutical ingredients and excipients affecting bioavailability: Impact on bioequivalence

The aim of the present paper is to illustrate the impact that excipients may have on the bioavailability of drugs and to review existing US-FDA, WHO and EMA regulatory guidelines on this topic. The first examples illustrate that small amounts of sorbitol (7, 50 or 60mg) affect the bioavailability of risperidone, a class I drug, oral solution, in contrast to what is stated in the US-FDA guidance. Another example suggests, in contrast to what is stated in the US-FDA BCS biowaivers guideline, that a small amount of sodium lauryl sulphate (SLS) (3.64mg) affects the bioavailability of risperidone tablets, although the reference product also includes SLS in an amount within the normal range for that type of dosage form. These factors are considered sufficient to ensure that excipients do not affect bioavailability according to the WHO guideline. The alternative criterion, defined in the WHO guideline and used in the FIP BCS biowaivers monographs, that asserts that excipients present in generic products of the ICH countries do not affect bioavailability if used in normal amounts, is shown to be incorrect with an example of alendronate (a class III drug) tablets, where 4mg of SLS increases bioavailability more than 5-fold, although a generic product in the USA contains SLS. Finally, another example illustrates that a 2mg difference in SLS may affect bioavailability of a generic product of a class II drug, even if SLS is contained in the comparator product, and in all cases its amount was within the normal range. Therefore, waivers of in vivo bioequivalence studies (e.g., BCS biowaivers, waivers of certain dosage forms in solution at the time of administration and variations in the excipient composition) should be assessed more cautiously.

Pharmacoeconomics of depot antipsychotics for treating chronic schizophrenia in Sweden

Aims: To determine the cost-effectiveness of long-acting injectable (LAI) antipsychotics for chronic schizophrenia in Sweden. Methods: A 1-year decision tree was developed for Sweden using published data and expert opinion. Five treatment strategies lasting 1 year were compared: paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol decanoate (HAL-LAI) and olanzapine tablets (oral-OLZ). Patients intolerant/failing drugs switched to another depot; subsequent failures received clozapine. Resources and employment time lost (indirect costs) were costed in 2011 Swedish kroner (SEK), from standard government lists. The model calculated the average cost/patient and quality-adjusted life-years (QALYs), which were combined into incremental cost-effectiveness ratios. Multivariate and 1-way sensitivity analyses tested model stability. Results: PP-LAI followed by OLZ-LAI had the lowest cost/patient (189,696 SEK) and highest QALYs (0.817), dominating in the base case. OLZ-LAI followed by PP-LAI cost 229,775 SEK (0.812 QALY), RIS-LAI followed by HAL-LAI cost 221,062 SEK (0.804 QALY), HAL-LAI followed by oral-OLZ cost 243,411 SEK (0.776 QALY), and oral-OLZ followed by HAL-LAI cost 249,422 SEK (0.773 QALY). The greatest proportions of costs (52.5–83.8%) were for institutional care; indirect costs were minor (2.4–3.8%). Results were sensitive to adherence and hospitalization rates, but not drug cost. PP-LAI followed by OLZ-LAI dominated OLZ-LAI followed by PP-LAI in 59.4% of simulations, RIS-LAI followed by HAL-LAI in 65.8%, HAL-LAI followed by oral-OLZ in 94.0% and oral-OLZ followed by HAL-LAI in 95.9%; PP-LAI followed by OLZ-LAI was dominated in 1.1% of the 40,000 iterations. Conclusion: PP-LAI followed by OLZ-LAI was cost-effective in Sweden for chronic schizophrenia and cost-saving overall to the healthcare system.

Bioequivalence and Pharmacokinetic Evaluation of Two Formulations of Risperidone 2 mg

BackgroundRisperidone is a benzisoxazole derivate and is effective in the treatment of schizophrenia and other psychiatric illnesses in adults and children. Although there are a few reports in the literature regarding the pharmacokinetic characteristics of risperidone, insufficient data on its pharmacokinetic properties in a Chinese population are available.ObjectiveTo meet the requirements for marketing a new generic product, this study was designed to compare the pharmacokinetic properties and bioequivalence of two 2 mg tablet formulations of risperidone: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult male Chinese volunteers.MethodsA single-dose, open-label, randomized-sequence, 2 × 2 crossover study was conducted in fasted healthy male Chinese volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test formulation (Risperidone tablet; Dr. Reddy’s Laboratories Ltd., Hyderabad, India) or the reference formulation (Risperdal® tablet; Xian-Janssen Pharmaceutical Ltd., Xi-an, China), followed by a 2-week washout period and subsequent administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 96 hours. Plasma concentrations of the parent drug, risperidone, and its active metabolite, 9-hydroxy-risperidone, were analyzed by a liquid chromatography–tandem mass spectrometry method. The formulations would be considered bioequivalent if the 90% confidence intervals (CIs) of the natural log-transformed values were within the predetermined 80–125% equivalence range for the maximum plasma drug concentration (Cmax) and the area under the plasma concentration–time curve (AUC), in accordance with guidelines issued by the US Food and Drug Administration. Assessment of tolerability was based on recording of adverse events (AEs), monitoring of vital signs, electrocardiograms, and laboratory tests at baseline and at completion of the study.ResultsA total of 24 healthy male Chinese volunteers (mean age 22.9 years [standard deviation (SD) 2.7, range 19.2–27.1]; weight 63.2 kg [SD 7.0, range 52.0–78.0]; and height 171.3 cm [SD 6.1, range 162.0–187.0]) were enrolled, and all completed the study. For the parent drug, risperidone, the 90% CIs of the relative values (test vs. reference) of the Cmax, AUC from time zero to time t (AUCt), and AUC from time zero to infinity (AUC∞) were 97.0–124.0%, 92.7–115.1%, and 92.8–114.2%, respectively. For the active metabolite, 9-hydroxy-risperidone, the values were 104.4–117.7%, 101.0–113.7%, and 100.4–113.4%, respectively. The two formulations met the predetermined criteria for bioequivalence. A total of 73 AEs were observed in 24 subjects during the study. The most common AE was sedation (48 events), followed by nasal reactions (14 events), postural hypotension (3 events), hypertriglyceridemia (2 events), dizziness (4 events), nausea (1 event), and anorexia (1 event). Their severity was as follows: 16 were mild, 57 were moderate, and none were severe. The majority of the AEs were considered to be related (48 events) or probably related (23 events) to the study medication. No clinically significant abnormalities on physical examination, vital sign measurements, or electrocardiographic recordings were reported. No serious AEs were reported.ConclusionsThe data from this study in healthy adult male Chinese subjects suggest that the test formulation met the regulatory criteria for bioequivalence to the reference formulation, on the basis of the rate and extent of absorption. Both formulations were well tolerated.

The results of the Tokyo Trial of Prevention of Post-ERCP Pancreatitis with Risperidone (Tokyo P3R): a multicenter, randomized, phase II, non-placebo-controlled trial

A previous study suggested that ulinastatin effectively prevented post-ERCP pancreatitis (PEP) and hyperenzymemia (PEH) in patients at average risk. In experimental models, risperidone, a selective serotonin 2A antagonist, ameliorated acute pancreatitis. We assessed the effect of risperidone combined with ulinastatin for the prevention of PEP in high-risk patients. In a multicenter, randomized, controlled, phase II trial, patients undergoing therapeutic ERCP were randomly assigned to receive ulinastatin (150000U) with or without risperidone (1mg). A risperidone tablet was taken orally 30-60min before ERCP and ulinastatin was administered intravenously for 10min immediately prior to ERCP. The primary end point was the incidence of PEP; secondary end points were PEH severity and enzyme levels (amylase, pancreatic amylase, lipase). A total of 226 patients (113 per group) were included in the study. Six patients in the risperidone+ulinastatin group and ten patients in the ulinastatin group developed pancreatitis (5.3 vs. 8.8%, p=0.438). The incidence of moderate/severe PEP was lower in the risperidone+ulinastatin group (1.8%) than in the ulinastatin group (4.4%), but this difference was not significant. Although the incidence of PEH did not differ significantly, post-ERCP levels of all pancreatic enzymes were significantly lower in the risperidone+ulinastatin group. Prophylactic oral risperidone administration in combination with ulinastatin did not reduce the incidence and severity of PEP in high-risk patients as compared with ulinastatin alone. However, risperidone showed an additive effect with ulinastatin, reducing serum pancreatic enzyme levels.

Content uniformity testing: suitability of different approaches for marketed low dose tablets

Context: Content uniformity (CU) testing was developed and improved to control the effectiveness and safety of dosage units. Many modifications of compendial CU test have been introduced and several alternatives have been suggested.Objectives: This study aims to evaluate the degree of suitability of current USP CU test for low dose tablets and to compare the performance of the current test with that of the former USP27-NF22 and other alternatives for different sample sizes.Methods: All locally marketed risperidone (RSP) tablets were analyzed using newly developed and validated isocratic UPLC method. The CU results were statistically analyzed in groups with sample sizes comparable to the USP sampling plans.Results: Seven out of eleven products failed the different requirements of the former and current USP <905>chapters as well as of several alternative CU tests with several substantial deviations.Conclusion: The current USP <905> chapter was found to have some deficiencies that allowed such failed products to exist in the market. The dependence of compendial CU test on two-staged sampling plan and the use of arithmetic mean to calculate the reference and acceptance values were obvious shortcomings.

Asterixis (Flapping Tremors) As an Outcome of Complex Psychotropic Drug Interaction

Asterixis (Flapping Tremors) As an Outcome of Complex Psychotropic Drug Interaction

P-1223 - Schizophrenia: switching from any oral antypsychotics to RLAI, a good solution to avoid relapses

Introduction The long term treatment of schizophrenia must fulfill some medical and functional needs, like: good tolerability for a long time administration, maintaining and improving the patient's psychiatric condition obtained previously and keeping at good levels overall patient's functionality. Objectives Most atypical antipsychotics are effective in the acute phase of schizophrenia, but on long term, the compliance of the patient could get worse due to big amount of tablets, side effects, stigma, diminished ability to think or concentrate, sedation, increase of BMI or prolactin. Aims To improve patients' compliance by switching from oral treatment to RLAI (Risperidone Long Acting Injection) and keep them away from relapses. Methods We evaluated 2 patients: first, 26 years, stabilized with risperidone tablets, 8 mg/day; second, 29 years, treated with amisulpride 800 mg/day, both having previously relapses after refusing to take their tablets. We switched them on a treatment with RLAI 50 mg/i.m., twice a month. Evaluations were made weekly during the 6 weeks of stabilization period and a follow-up for a period of 6 months. The well-being of the patient was evaluated by using the following scales: PANSS, CGI-S, CGI-I, the patients' satisfaction with PSMQ questionnaire and activity with WPAI-GH. Results 1) There was none relapse for both patients. 2) We did not use any corrective co-medication. 3) The patients' satisfaction was greater and the functionality was better, due to a good compliance and fewer side-effects. Conclusions Switching from another antipsychotic to RLAI is a good solution to improve the patients compliance, functionality and quality of life overall.

Effect of risperidone tablets on brain metabolite ratios in male first-episode schizophrenia: relationship with treatment response

Objective To identify the metabolite levels and to study the potential effects of risporidone tablets on prefrontal lobe and thalamus in male first-episode schizophrenia by proton magnetic resonance spectroscopy (1H-MRS).Methods Twenty-two male first-episode schizophrenics were examined at prefrontal lobe and thalamus by multi-voxel 1H-MRS before and after 8 weeks' risperidone tablets treatment,and 30 normal controls were assessed once.The patients were also received positive and negative syndrome scale(PANSS) and Wisconsin card sorting test (WCST) before and after treatment.The N-aeetylaspartate ( NAA ),Choline-congtaining compounds (Cho),and Creatine compounds (Cr) were measured and the ratios of NAA/Cr,Cho/Cr were determined.Results On left prefrontal lobe and left thalamus,the NAA/Cr ratio in patients before treatment demonstrated lower than those in normal controls ( ( 1.37 ± 0.33 ) vs ( 1.61 ± 0.38 ),t =2.57,P ＜ 0.05 ; ( 1.46 ± 0.35 ) vs ( 1.71 ± 0.38 ),t =2.36,P ＜ 0.05 ).There were no significant differences in both the ratios of NAA/Cr and Cho/Cr between pre- and post-treatment (P＞0.05 ).The changes of NAA/Cr on left prefrontal lobe post-treatment were negatively related with the alterations of the total score of PANSS ( r =- 0.46,P ＜ 0.05 ),the score of negative symptoms ( r =- 0.48,P ＜ 0.05 ),the responses errors ( r =- 0.42,P ＜ 0.05 ) and the porseverative errors ( r =- 0.40,P ＜ 0.05 ),meanwhile,positively related with the alterations of the categories completed ( r =0.44,P ＜0.05 ) and the conceptual level responses ( r =0.42,P ＜ 0.05 ).Conclusions Abnormalities in neuronal function and/or integrity presented on prefrontal lobe and thalamus maybe exist in male first-episode schizophrenics.Short-term antipsvchotic treatment with risperidone tablets may have no effects on measures of prefrontal lobe and thalamus. Key words: First-episode Schizophrenia; Male; Risperidone; Magnetic Resonance Spectroscopy

Relative bioavailability and pharmacokinetic comparison of two 2-mg risperidone tablet formulations: A single dose, randomized-sequence, double-blind, 2-way crossover study in healthy male volunteers in thailand

Background: Data regarding the pharmacokinetic properties of risperidone in the Thai population are limited. A new generic tablet formulation was recently developed, but bioequivalence research is necessary to obtain marketing authorization for it in Thailand. Objective: The aim of this study was to evaluate and compare the pharmacokinetic properties of risperidone and its active metabolite, 9-hydroxyrisperidone (which reportedly contributes to the drug's pharmacodynamic effects), in a newly developed generic tablet formulation (test) and a branded formulation (reference) in healthy, fasting, male Thai volunteers. Methods: A single-dose, randomized-sequence, doubleblind, 2-way crossover design was used in this study. The study took place from October 21 through November 28, 2007. After a ≥10-hour overnight fast, volunteers were orally administered one 2-mg risperidone tablet, either the test formulation (Condrug International Company, Ltd.) or the reference formulation—according to the randomization schedule—followed by a 14-day washout period and administration of the alternate formulation. Blood samples were collected over a period of 96 hours. Risperidone and 9-hydroxyrisperidone plasma concentrations were simultaneously determined using a validated HPLC/ion trap mass spectrometry method. The plasma concentration-time curves of the active moiety, risperidone, and 9-hydroxyrisperidone were generated for each volunteer, from which the C max, T max, AUC 0-last, AUC 0-∞, and t ½ were determined using noncompart-mental analysis. The effects of formulation, period, sequence, and subject (within sequence) on pharmacokinetic parameters were analyzed using ANOVA. According to regulatory requirements set forth by Thailand, the Association of Southeast Asian Nations, and the US Food and Drug Administration, products meet the criteria for bioequivalence if the 90% CIs of the treatment ratios for C max and AUC are within the range of 0.80 to 1.25. Tolerability was assessed by patient interview, monitoring vital signs (ie, resting blood pressure, heart rate, body temperature), physical examination, and laboratory tests (ie, urinalysis, hematology, blood chemistry) before and after the study. Results: A total of 22 Thai male volunteers (mean [SD] age, 28.18 [8.27] years [range, 20.62–44.19 years]; weight, 62.43 [4.76] kg [range, 55.03–76.02 kg]; and body mass index, 21.76 [2.07] kg/m 2 [range, 18.9924.91 kg/m 2]) completed the study. The mean (SD) relative bioavailabilities of test to reference formulations determined from AUC of the active moiety, risperidone, and 9-hydroxyrisperidone were 1.06 (0.18), 1.07 (0.29), and 1.04 (0.17), respectively. The ANOVA suggested no statistically significant effect of formulation, period, or sequence on the studied pharmacokinetic parameters of the active moiety, risperidone, or 9-hydroxyrisperidone. The 90% CIs for the natural logarithm-transformed ratios of C max, AUC 0-last, and AUC 0-∞ were as follows: for active moiety, 0.94 to 1.03, 0.98 to 1.11, and 0.98 to 1.10, respectively; for risperidone, 0.90 to 1.10, 0.96 to 1.13, and 0.96 to 1.14, respectively; and for 9-hydroxyrisperidone, 0.91 to 1.03, 0.97 to 1.10, and 0.96 to 1.09, respectively. All met the criteria for bioequivalence. The most commonly reported adverse events (AEs) were somnolence (100.0%), orthostatic hypotension (13.6%), headache (4.5%), and syncope (2.3%). AEs were mild and disappeared within 1 day. No volunteers withdrew from the study because of AEs. Conclusions: The single-dose pharmacokinetic data in this small, all-male, selected sample of fasting, healthy volunteers met Thailand's regulatory criteria for assuming bioequivalence of the tested generic and reference 2-mg risperidone tablets. Both formulations were well tolerated.

A comparison of serum prolactin concentrations after administration of paliperidone extended-release and risperidone tablets in patients with schizophrenia

Increases in serum prolactin concentrations after administration of risperidone have been attributed, by some, to the availability of paliperidone in plasma. This double-blind, randomized, parallel-group study in patients with schizophrenia compared serum prolactin concentrations following the administration of paliperidone extended-release and risperidone immediate-release tablets. At steady state, the doses administered resulted in a similar exposure to paliperidone and the pharmacologically active fraction of risperidone (i.e. risperidone + paliperidone), respectively. Eligible patients were randomized to either paliperidone extended-release 12 mg on days 1-6 or risperidone immediate-release 2 mg on day 1 and 4 mg on days 2-6. Mean serum prolactin concentrations increased on day 1 (C(max): 71.8 ng/ml and 89.7 ng/ml reached at 6.5 hours and 2.6 hours for paliperidone extended-release and risperidone immediate-release, respectively). On day 6, serum prolactin concentration-time profiles were similar for both treatments, with overall higher serum prolactin concentrations than on day 1 (AUC(0-24 h): 1389 and 842 ng h/ml, and 1306 and 741 ng.h/ml on day 6 and day 1 for paliperidone extended-release and risperidone immediate-release, respectively). These results indicate that paliperidone extended-release 12 mg and risperidone immediate-release 4 mg, administered over a period of 6 days, lead to similar elevations in serum prolactin concentrations.