• Korean Journal of Biological Psychiatry
• /
• v.10 no.2
• /
• pp.107-115
• /
• 2003

Objective:The purpose of this study was to know about the mechanism of pathogenesis of type 2 diabetes mellitus by using of blood glucose, glucoregulatory factor, insulin resistance in schizophrenic patients receiving antipsychotics. Method:Modified oral glucose tolerance tests were performed in 20 schizophrenic patients receiving haloperidol, risperidone and olanzapine. Insulin, glucagon, C-peptide and cortisol were measured in 0, 15, 45, 75 minutes after glucose loading, and insulin resistance was calculated by HOMA(homeostasis model assessment) method. Result:Olanzapine-treated patients had significant glucose elevation 45 minutes after glucose challenge. Also modest increases in HOMA IR values were detected in patients treated with olanzapine. Conclusion:Olanzapine treatment of non-diabetic patients with schizophrenia can be associated with type 2 diabetes mellitus through the elevation of glucose and insulin resistance. Elevated insulin resistance may be a causative mechanism of type 2 diabetes mellitus in patients receiving olanzapine.

• Journal of Pharmaceutical Investigation
• /
• v.40 no.5
• /
• pp.297-304
• /
• 2010

The present work focuses on preparation of olanzapine, orally dispersing tablets by direct compression method. Effect of super disintegrant crospovidone, disintegration time, drug content on in vitro release has been studied. A factorial design was employed in formulating a prompt dispersible tablet. The selected independent variables crospovidone and fmelt showed significant effect on dependent variables i.e. disintegration time and percent drug dissolved. Disintegration time and percent drug dissolved decreased with increase in the level of crospovidone. The similarity factor $f_2$ was found to be 97.48 for the developed formulation indicating the release was similar to that of the marketed formulation. Pharmacokinetics of olanzapine after single-dose oral administration of orally disintegrating tablet in normal volunteers were evaluated and the results showed that PK parameters (Cmax, Tmax, AUC) of the designed ODT matrix were similar to those of commercial product, Zyprexa Zydis$^{(R)}$ as a reference.

• Korean Journal of Biological Psychiatry
• /
• v.6 no.2
• /
• pp.240-245
• /
• 1999

Object : This study was designed to evaluate the effects of olanzapine on the schedule-induced polydipsia(SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered olanzapine as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol for the dopamine antagonist to rats which showed schedule-induced polydipsic behavior. Methods : Spraque-Dawley rats weighing 200-250gm were individually housed and maintained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds(FT-60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior(greater than 3 times of water per session on average). 5 groups of rats were administered olanzapine(3mg/kg, i.p), olanzapine(10mg/kg, i.p), fluoxetine(5mg/kg, i.p.), haloperidol(0.1mg/kg, i.p.), and vehicle(1cc/kg, i.p.) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a posthoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats(N=8) were individually housed and given a single bolus(14.5gm) of food per day which maintained them at their average body weight. Results and Conclusion : The results were as follows ; 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake over the 3 weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 3mg group showed significant decrease in the amount of water intake at 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 10mg group showed significant decrease in the amount of water intake at 2nd and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their average amount of polydipsic water intakes. 3) The fluoxetine group showed significantly lower amounts of water intake than the haloperidol group at 2nd weeks of drug treatment. And also the fluoxetine group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. The olanzapine 3mg group and the olanzapine 10mg group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. Above findings suggest that the fixed time feeding procedure for schedule-induced polydipsia as an animal model of obsessive compulsive disorder was effective to the evaluation of pharmacological challenge study. The authors assume that the serotonin hypothesis and the serotonin-dopamine interaction hypothesis are preferred to the dopamine hypothesis in the biological etiology of obsessive-compulsive disorder.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.22
• /
• pp.9587-9592
• /
• 2014

Nausea and vomiting are common adverse events in chemotherapy. In spite of the serious effects on the quality of life and further treatment, they remain overlooked by physicians, and no standard treatment has been developed. Neurokinin-1 (NK-1) receptor antagonists and palonosetron are the major agents in the standard regimen for treating moderately and highly emetogenic chemotherapy-induced nausea and vomiting (CINV). However, NK-1 receptor antagonists first became commercially available at the end of 2013 and palonosetron has not been extensively applied in China. Olanzapine was recommended as a therapy for moderate and severe CINV in antiemesis-clinical practice guidelines in oncology in 2014 for the first time. It is an atypical antipsychotic agent, which can block multiple receptors on neurotransmitters. During more than 10 years, olanzapine has demonstrated significant effects in preventing CINV and treating breakthrough and refractor CINV, which was observed in case reports, precise retrospective studies, and phase I, II and III clinical trials, with no grade 3 to 4 adverse events. In particular, it is superior to aprepitant and dexamethasone in delayed nausea and vomiting. Therefore, this compound is worthy of further investigation.

• Korean Journal of Clinical Pharmacy
• /
• v.28 no.3
• /
• pp.204-215
• /
• 2018

Background: In this systematic review and meta-analysis, the effect of metformin on weight loss was assessed to determine whether metformin should be recommended for the prevention or treatment of weight gain in patients receiving antipsychotic medication for the treatment of schizophrenia or schizoaffective disorder. Methods: The PubMed, Embase, and Cochrane Library databases were searched for all published randomized controlled trials (RCTs) from inception to June 2018. In addition, the references of relevant articles were also examined. Using Review Manager 5, the pooled estimates of the weighted mean difference (WMD) of the changes in body weight and body mass index (BMI) and the corresponding 95 % confidence intervals (CIs) were calculated. Results: The meta-analysis included 15 RCTs. The pooled analysis showed that compared with placebo, metformin led to significant reductions in body weight (WMD: -2.09, 95% CI: -2.59, -1.60; p<0.00001) and BMI (WMD: -0.90, 95% CI: -1.08, -0.72; p<0.00001). The effect of metformin on weight loss was greater in patients receiving olanzapine than in patients receiving clozapine (body weight, WMD: -2.39, 95% CI: -3.76, -1.02; p=0.0006 for olanzapine; -1.99, 95% C: -3.47, -0.51; p=0.009 for clozapine; BMI, WMD: -1.15, 95% CI: -1.74, -0.57, p=0.0001 for olanzapine; WMD: 0.76, 95% CI: -1.23, -0.28; p=0.002 for clozapine). Conclusion: Metformin can be recommended to manage olanzapine-induced weight gain in patients with schizophrenia or schizoaffective disorder. The magnitude of the reductionss in body weight and BMI implieds that the use of metformin to attenuate olanzapine-induced weight gain can minimize the risk of coronary heart disease.

• The Korean Journal of Nuclear Medicine
• /
• v.36 no.4
• /
• pp.224-231
• /
• 2002

Purpose: This pilot study was performed to understand the pharmacological effect of olanzapine, an atypical antipsychotic agent, on dopamine transporter in schizophrenic patients. Materials and Methods: Six patients (3 male, 3 female) with schizophrenia, who had not taken any psychotropic drugs for at least four weeks, were studied. Nuclear imaging using $[^{123}I]-{\beta}-CIT$ SPECT was obtained before and after 4-week treatment with olanzapine. Analysis of ROI on the striatum, caudate nucleus, and putamen was performed. Results: Post-treatment uptake was significantly increased in all the ROIs compared with pre-treatment uptake. Conclusion: This preliminary study with the small number of schizophrenic patients suggested an increase in uptake of dopamine transporter in the striatum, caudate nucleus, and putamen after 4-week treatment with olanzapine, which warrants a large-scaled controlled study to confirm the current findings.

• Archives of Pharmacal Research
• /
• v.26 no.11
• /
• pp.951-959
• /
• 2003

A series of typical (chlorpromazine, haloperidol and thioridazine) and atypical (risperidone, quetiapine, clozapine and olanzapine) antipsychotics were tested for effects on integrated bioenergetic functions of isolated rat liver mitochondria. Polarographic measurement of oxygen consumption in freshly isolated mitochondria showed that electron transfer activity at respiratory complex I is inhibited by chlorpromazine, haloperidol, risperidone, and quetiapine, but not by clozapine, olanzapine, or thioridazine. Chlorpromazine and thioridazine act as modest uncouplers of oxidative phosphorylation. The typical neuroleptics inhibited NADH-coenzyme Q reductase in freeze-thawed mitochondria, which is a direct measure of complex I enzyme activity. The inhibition of NADH-coenzyme Q reductase activity by the atypicals risperidone and quetiapine was 2-4 fold less than that for the typical neuroleptics. Clozapine and olanzapine had only slight effects on NADH-coenzyme Q reductase activity, even at 200 $\mu$ M. The relative potencies of these neuroleptic drugs as inhibitors of mitochondrial bioenergetic function is similar to their relative potencies as risk factors in the reported incidence of extrapyramidal symptoms, including tardive dyskinesia (TD). This suggests that compromised bioenergetic function may be involved in the cellular pathology underlying TD.

• Journal of The Korean Society of Clinical Toxicology
• /
• v.7 no.1
• /
• pp.44-46
• /
• 2009

Herein, we report a case of emergency cesarean section after severe maternal drug intoxication in late pregnancy. At a 38-week-gestation, a 32-year-old woman with a 10-year history of bipolar disorder took olanzapine (200 mg), diazepam (20 mg), and zolpidem (200 mg) as part of a suicidal attempt. Given her unconscious state and the evident concern regarding the toxic effects of the drugs on the fetus, a cesarean section was performed immediately. The patient gave birth to a male baby with Apgar scores of 5 at 1 and 8 at 5 minutes. The baby showed dyspnea and decreased activity directly after birth. After supportive care, the condition of both mother and baby improved and both were discharged.

• 한국임상약학회:학술대회논문집
• /
• 2007.12a
• /
• pp.178-178
• /
• 2007

• Molecular & Cellular Toxicology
• /
• v.3 no.2
• /
• pp.127-131
• /
• 2007

Chronic treatment with olanzapine (OLZ), an atypical antipsychotic drug, is associated with the adverse effects of weight gain, hyperglycemia and/or hypertriglyceridemia. Green tea or epigallocatechin gallate (EGCG), one of the most abundant green tea polyphenols, significantly reduces or prevents an increase in glucose levels, lipid markers and/or body weight. We hypothesized that combined treatment with OLZ and green tea extract (GTE) or EGCG may prevent body weight gain and increase of the lipid markers. ICR male mice weighing an average of 30.51 g (n=32) at the beginning of the experiment were used. OLZ, OLZ+GTE and OLZ+EGCG were administered for 27 d in the drinking water, and then the levels of fasting glucose, nitric oxide (NO), and a typical lipid marker triglyceride (TG) were determined in plasma. The body weight and food intake were also compared. The chronic treatment of OLZ increased the average body weight compared with that of controls. In the presence of GTE or EGCG, the OLZ-induced increase in body weight was significantly prevented. Furthermore, in the OLZ group, the plasma levels of glucose, NO and TG were significantly increased, whereas GTE or EGCG prevented these increases. These results implicate that OLZ may induce systematic inflammatory reaction, and suggest that GTE or EGCG can protect against OLZinduced weight gain, hyperglycemia and hypertriglyceridemia.