• Archives of Pharmacal Research
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• v.29 no.6
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• pp.525-533
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• 2006

The aim of this study was to evaluate the bioequivalence of risperidone in healthy male subjects representing different CYP2D6 genotypes with respect to risperidone, 9-hydroxyrisperidone (9-OH-risperidone), and active moiety. A total of 506 Korean subjects were genotyped for $CYP2D6^*10$ by means of allele-specific polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Based on the genotype analysis, 24 subjects, 7 homozygous for $CYP2D6^*1$ for $^*10$, and 7 heterozygous for $^*10$, were recruited and received a single oral dose of 2 mg risperidone tablet in this study. Serum concentrations of risperidone and 9-OH-risperidone up to 48 h were simultaneously determined. There were no significant differences of the active moiety, risperidone, and 9-OH-risperidone between the two preparations in AUC_{0-{\propto}}$ and $C_{max}$. The 90% confidence intervals (Cls) for the ratio of means of the log-trans-formed AUC_{0-{\propto}}$ and $C_{max}$ for the active moiety, risperidone, and 9-OH-risperidone were all within the bioequivalence acceptance criteria of 0.80-1.25. The $CYP2D6^*10$ allele particularly was associated with higher serum concentrations of risperidone and the risperidone/9-OH-risperidone ratio compared with the $CYP2D6^*1$ allele. The results demonstrate that the two preparations of risperidone are bioequivalent and it can be assumed that they are therapeutically equivalent and exchangeable in clinical practice. Furthermore, the pharmacokinetic parameters of risperidone and the risperidone/9-OH-risperidone ratio are highly dependent on the CYP2D6 genotypes.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.93-93
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• 1993

도파민 D 수용체 및 5-HT 수용체 차단기전을 지닌 새로운 항정신분열증 약물인 risperidone은 활성형 대사물로 9-OH risperidone을 체내에서 생성하는 바, 이 대사과정의 유전적 다형성의 여부 즉 hydroxylation 과정에 CYPIID6의 관여 여부를 검토코자 하였다. Metoprolol 100 mg 경구투여로 CYPIID6의 대사능의 표현형을 결정한 12명의 정상 피험자(11명: extensive metabolizer, 1명: poor metabolizer)를 대상으로 하였으며, 피험자는 risperidone 1 또는 2 mg 경구투여후 혈중 risperidone 및 9-OH risperidone 농도를 경시적으로 radioimmunoassay법으로 측정하였다. 이들 피험자중 6명의 extensive metabolizer는 quinidine 600 mg/day의 용량 투여로 CYPIID6의 활성도를 완전 억제시킨 후 risperidone 1 mg 경구투여에 따른 약동학적 성상을 재검토하여 risperidone hydroxylation에 CYPIID6의 관여 여부를 검토하였다. 1) 1명의 poor metabolizer는 extensive metabolizer에 비해 현저히 긴 risperidone 반감기를 보였다. 2) 12명의 피험자에서 관찰된 metoprolol metabolic ratio는 risperidone 혈장 반감기 및 log(risperidone AUC/9-OH-risperidone AUC)와 유의한 상관성을 나타내었다. 3) Quinidine 투여는 risperidone의 반감기의 유의한 증가와 9OH risperidone AUC의 현저한 감소를 보였으나, 9-hydroxylation 대사과정이 완전히 억제되지는 않았다.

• Korean Journal of Biological Psychiatry
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• v.7 no.2
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• pp.198-205
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• 2000

Objectives : Risperidone and clozapine belong to a new generation of antipsychotics that are reportedly more effective and better tolerated than conventional neuroleptics. However, each of these agents costs far more per unit than conventional neuroleptics. The purpose of our retrospective study was to ascertain the total cost and effectiveness of treatment before and after administration of risperidone and clozapine in "revolving door" schizophrenia patients. Method : Data collected on revolving door schizophrenics for 2 years before clozapine and risperidone treatment and for at least 2 years after clozapine and risperidone treatment. Direct cost of inpatient and outpatient treatment was measured. Effectiveness was scaled as "years of mild disability gained". Result : Both risperidone and cloazpine result in higher costs and additional benefits to patients, for example, increased mild disability, reduced number of relapse, and reduced hospital length-of-stay. An ICER of risperidone was less than Rc and ICER of clozapine was greater than Rc. According to decision-analytic this model, risperidone had favorable cost-effectiveness ratios relative to clozapine. Conclusion : We have assumed that risperidone is more cost-effective than clozapine.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.165-165
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• 1993

목적:지금까지 Risperidone의 치료 효능과 안전성에 대한 연구들이 모두 만성 정신분열병 환자들만을 대상으로 이루어졌고, 효율적인 약물 요법의 중요한 지침이 되는 유효치료용량(effective therapeutic dosage)에 대한 연구가 이루어지지 않고 있는 바, 본 연구에서는 초발인 급성 정신분열병 환자들을 대상으로 첫째, Risperidone의 항정신병 효과(antipsychotic effect)와 추체외로계증상(extrapyramidal symptoms)을 평가하고 둘째, Risperidone의 항정신병 효과와 혈장 Risperidone 및 9-hydroxyrisperidone 농도와의 상관관계를 분석하여 유효혈장농도(therapeutic dose range)와 유효치료용량(effective therapeutic dosage)의 존재 여부를 검토코자 한다. 방법: DSM-III-R 진단기준(APA 1987)예 의해 정신분열병형 장애로 진단된 환자 11명(남자 5, 여자 6)을 대상으로 Risperidone을 이중맹검법(double blind design)으로 6주간 투약하였다. 정신병리의 평가는 PANSS(Kay 1988)를 이용하였고 추체외로계 부작용의 평가는 ESRS(Chouinard 1980)를 이용하였다. 혈장 Risperidone 농도와 혈장 9-hydroxyrisperidone 농도는 Jansen사의 Radioimmunoassay Kit를 이용하여 3회 측정하였다. 결과: PANSS 점수는 Risperidone 투여 후 1주째부터 통계적으로 유의하게 감소하였다. Parkinsonism과 dyskinesa에 대한 physician's examination 점수는 전체 연구 기간 동안 유의한 변화를 보이지 않았다. Dystonia에 대한 physician's examination 점수는 Risperidone 투여 후 1주째에는 평균 5.96점으로 높았으나 2주째부터 통계적으로 유의하게 감소되어 6주째에는 유지되었다. 혈장 Risperidone 농도와 혈장 9-hydroxyrisperidone 농도는 PANSS 점수와 유의한 상관관계를 보이지 않았다.

• Korean Journal of Biological Psychiatry
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• v.7 no.1
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• pp.74-79
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• 2000

Objectives : The dopamine-blocking effects and the associated side effects(amenorrhea, lactation, sexual dysfunction) of classical antipsychotics in schizophrenic patients have been studied for a long time. The purpose of this study was to find out these effects of new antipsychotics(risperidone, olanzapine) in schizophrenic patients treated with clinically relevant doses. Method : Plasma levels of both prolactin and testosterone were measured in 91 schizophrenic patients(28 taking haloperidol, 4-20mg/day ; 31 taking risperidone, 2-6mg/day ; 32 taking olanzapine, 5-20mg/day). Results : In male schizophrenic patients, the prolactin levels of risperidone group($76.44{\pm}38.85ng/ml$) and haloperidol group($60.26{\pm}20.74ng/ml$) had no significant difference, but were significantly higher than that of olanzapine($26.90{\pm}5.36ng/ml$). In female, the prolactin level of olanzapine group($36.66{\pm}17.55$) was significantly lower than those of risperidone($121.7{\pm}48.33$) and haloperidol group($161.66{\pm}37.53$). And prolactin level of risperidone group was lower than that of haloperidol group. While the testosterone plasma level of risperidone, haloperidol and olanzapine in both male and female schizophrenic patients had no significant difference. Conclusions : At doses known to be effective in popular clinical setting, prolactin level in patients taking risperidone was higher than that of haloperidol, while olanzapine showed no significant difference in terms of prolactin plasma level from haloperidol. New antipsychotics may not influence the testosterone plasma level.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.16 no.2
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• pp.239-250
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• 2005

Objective : The purpose of this study was obtaining data on the efficacy and safety of risperidone in child and adolescent psychiatric patients. Method : Thirty one children and adolescents (males n=18, females n=13, age ranged from 5.4 to 17.3 years) treated with risperidone were selected among child and adolescent psychiatric inpatients of Seoul National University Hospital from January, 2001 to June, 2002, and charts for them were reviewed retrospectively. Results : The primary psychiatric disorders treated with risperidone were schizophrenia and other psychosis, bipolar I disorder with psychotic features, Tourette's disorder, autism spectrum disorders, mixed receptive and expressive language disorder, attention deficit-hyperactivity disorder, conduct disorder and obsessive-compulsive disorder. twelve of these had comorbid mental retardation. Primary target symptoms of risperidone were psychotic symptoms (n=13 or $41.9\%$), behavioral symptoms (n=10 or $32.3\%$) including aggression, impulsivity, hyperactivity, stereotypy nonresponsive to other psychiatric treatments, and chronic and severe tics (n=8, $25.8\%$). The efficacy of risperidone was measured by clinical global improvement (CGI) for target symptoms, $67.7\%$ of subjects showed moderate or marked improvements and its therapeutic effect appeared to be maintained during at least 7.5 months. Mean daily dosage of risperidone was $0.05{\pm}0.01mg/kg$, the group with psychotic symptoms had significantly higher mean daily dosage (0.07mg/kg) compared with other two groups (0.04mg/kg) with behavioral symptoms or tics. A variety of adverse events were reported in this study : weight gain (n=23) most commonly reported, extrapyramidal symptoms (n=15), autonomic symptoms (n=6), sedation (n=5) and symptoms related to hyperprolactinemia (n=2) etc. Although there was no drug change related to the adverse events of risperidone, and $90\%$ of subjects at their last visits were maintained on it, thus its tolerability appeared good. Conclusions Results suggest that risperidone may be relatively safe and effective drug in managing a wide variety of child and adolescent psychopathologies such as psychotic symptoms, behavioral symptoms including aggression, impulsivity, hyperactivity and stereotypy nonresponsive to other psychiatric treatments, and chronic and severe tics. Controlled and long-term studies of efficacy and safety of risperidone treatment for children and adolescents are recommended in the future.

• Korean Journal of Biological Psychiatry
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• v.11 no.2
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• pp.127-135
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• 2004

Object:The goal of this study was to examine the changes in body weight and glucose levels of the patients treated with risperidone, clozapine or haloperidol in order to compare the effect of risperidone or clozapine with that of haloperidol. Methods:For nine months(January to September, 2003), a prospective study was performed in 60 patients with chronic schizophrenia who were in Seoul National Hospital. Two-week period was required for a drug wash-out. The patients were randomly assigned to risperidone, clozapine and haloperidol groups. They were given risperidone(n=20), clozapine(n=20) and haloperidol(n=20), respectively, everyday for 12 weeks. To examine the effects of these drugs on body weight and fasting glucose levels, we measured body weight and glucose levels of all the patients first without the drug treatment and at each end of 4, 8, and 12-week periods with the treatment. And we examined the differences among three groups in the changes of body weight and fasting glucose levels. Results:There were no significant differences in the changes of the body weight and fasting glucose levels between the atypical antipsychotics(risperidone or clozapine) and the typical antipsychotics(haloperidol). Conclusion:The study in the patients with chronic schizophrenia suggests that risperidone or clozapine do not cause any additional effects on body weight or glucose levels compared to haloperidol.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.129-133
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• 1998

Objective : Base on clinical practice, the authors report a case of tardive dyskinesia arising during the course of treatment with resperidal. Methods : This article was review and analysis of a case on risperidone-induced tardive dyskinea. Results : Mrs K, a 51-year-old woman with a 1-year history of schizophrenic disorder, gradually developed tardive dyskinetic movement of the mouth, lip, and tongue over a 4 month period(From July, 1996 to June, 1997) while taking risperidone. Initially she was treated with haloperidol and alprazolam. However, the haloperidol was subsequently discontinued because of EPS developed. From 11th March, 1997, she was observed to have a severe form of tardive dyskinesia involving her tongue, lip, and mouth. After risperidone was withdrawn at 9th May 1997, her tardive dyskinetic movement was disappeared. Conclusions : This is, to our knowledge, the first report of the onset of tardive dyskinesia in a patient taking risperidone. However, additional controlled studies of specific questions are needed ; e.g., the dose-response curves for produce tardive dyskinesia and the mechanism of producing risperidone-induced tardive dyskinea and so on.

• Korean Journal of Biological Psychiatry
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• v.10 no.2
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• pp.141-146
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• 2003

Objective:To find out the optimal assessment that can relieve amenorrhea associated with risperidone. Methods:Sixteen female outpatients who have taken risperidone for more than 3 months reported voluntarily amenorrhea during Nov 2001 to May 2002. Since the reports of the amenorrhea, the resolution of amenorrhea has been prospectively followed during the next six months. The dosage of risperidone was reduced or discontinued in nine of sixteen patients, while risperidone was switched to olanzapine or quetiapine in other 7 patients according to the clinician's decision. Results:Fourteen of 16 patients showed higher levels of prolactin than normal level. Five patients of the risperidone-reduction group recovered from the amenorrhea while all subjects of the drug-switch group recovered. The resolved patients of the former group recovered from amenorrhea in the dosage below 3mg per day of risperidone. Two patients of the risperidone-reduction group were dropped out during the reduction. Conclusion:These findings suggest that risperidone-induced amenorrhea may be alleviated by reducing dosage to less 3mg per day(including discontinuation) or by switching to other antipsychotic drugs. Whether we would choose which method depends on patient's clinical status, diagnosis, and dose of medication and so on.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.138-141
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• 1998

Neuroleptic malignant syndrome (NMS) is an uncommon but potentially fatal idiosyncratic reaction to neuroleptics, characterized by muscular rigidity, fever, autonomic dysfunction, and altered consciousness. The major theories to explain NMS is central dopaminergic blockade, but it is unclear. Risperidone is a new antipsychotic drug, a benzisoxazole derivative that blocks dopamine $D_2$ receptor and serotonin type 2 receptor. The comparatively greater serotonin-blocking activity is believed to give risperidone the specific property of not causing any more extrapyramidal side effects than conventional antipsychotics at the optimal dose of 4-8mg/day. It is postulated that risperidone is unlikely to cause NMS. Here, we report a case of risperidone induced neuroleptic malignant syndrome.