lurasidone-hydrochloride and ziprasidone

The dose-response relationships of antipsychotic drugs for schizophrenia are not well defined, but such information would be important for decision making by clinicians. The authors sought to fill this gap by conducting dose-response meta-analyses.. A search of multiple electronic databases (through November 2018) was conducted for all placebo-controlled dose-finding studies for 20 second-generation antipsychotic drugs and haloperidol (oral and long-acting injectable, LAI) in people with acute schizophrenia symptoms. Dose-response curves were constructed with random-effects dose-response meta-analyses and a spline model. The outcome measure was total score reduction from baseline on the Positive and Negative Syndrome Scale or the Brief Psychiatric Rating Scale. The authors identified 95% effective doses, explored whether higher or lower doses than the currently licensed ones might be more appropriate, and derived dose equivalencies from the 95% effective doses.. Sixty-eight studies met the inclusion criteria. The 95% effective doses and the doses equivalent to 1 mg of oral risperidone, respectively, were as follows: amisulpride for patients with positive symptoms, 537 mg/day and 85.8 mg; aripiprazole, 11.5 mg/day and 1.8 mg; aripiprazole LAI (lauroxil), 463 mg every 4 weeks and 264 mg; asenapine, 15.0 mg/day and 2.4 mg; brexpiprazole, 3.36 mg/day and 0.54 mg; haloperidol, 6.3 mg/day and 1.01 mg; iloperidone, 20.13 mg/day and 3.2 mg; lurasidone, 147 mg/day and 23.5 mg; olanzapine, 15.2 mg/day and 2.4 mg; olanzapine LAI, 277 mg every 2 weeks and 3.2 mg; paliperidone, 13.4 mg/day and 2.1 mg; paliperidone LAI, 120 mg every 4 weeks and 1.53 mg; quetiapine, 482 mg/day and 77 mg; risperidone, 6.3 mg/day and 1 mg; risperidone LAI, 36.6 mg every 2 weeks and 0.42 mg; sertindole, 22.5 mg/day and 3.6 mg; and ziprasidone, 186 mg/day and 30 mg. For amisulpride and olanzapine, specific data for patients with predominant negative symptoms were available. The authors have made available on their web site a spreadsheet with this method and other updated methods that can be used to estimate dose equivalencies in practice.. In chronic schizophrenia patients with acute exacerbations, doses higher than the identified 95% effective doses may on average not provide more efficacy. For some drugs, higher than currently licensed doses might be tested in further trials, because their dose-response curves did not plateau.

Topics: Acute Disease; Administration, Oral; Antipsychotic Agents; Aripiprazole; Clozapine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Haloperidol; Humans; Imidazoles; Indoles; Isoxazoles; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Piperidines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Thiophenes

This systematic review provided a critical synthesis and a comprehensive overview of guidelines on the treatment of mixed states.. The MEDLINE/PubMed and EMBASE databases were systematically searched from inception to March 21st, 2018. International guidelines covering the treatment of mixed episodes, manic/hypomanic, or depressive episodes with mixed features were considered for inclusion. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II.. The final selection yielded six articles. Despite their heterogeneity, all guidelines agreed in interrupting an antidepressant monotherapy or adding mood-stabilizing medications. Olanzapine seemed to have the best evidence for acute mixed hypo/manic/depressive states and maintenance treatment. Aripiprazole and paliperidone were possible alternatives for acute hypo/manic mixed states. Lurasidone and ziprasidone were useful in acute mixed depression. Valproate was recommended for the prevention of new mixed episodes while lithium and quetiapine in preventing affective episodes of all polarities. Clozapine and electroconvulsive therapy were effective in refractory mixed episodes. The AGREE II overall assessment rate ranged between 42% and 92%, indicating different quality level of included guidelines.. The unmet needs for the mixed symptoms treatment were associated with diagnostic issues and limitations of previous research, particularly for maintenance treatment.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Electroconvulsive Therapy; Humans; Lithium; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Practice Guidelines as Topic; Quetiapine Fumarate; Thiazoles; Valproic Acid

Antipsychotics have serious metabolic side effects on blood glucose. However, the comparative influence of these drugs on blood glucose levels has not been comprehensively evaluated. We conducted a network meta-analysis to create a hierarchy of the side effects of 12 antipsychotic drugs on changes in blood glucose levels.. A systematic search of the PubMed, EMBASE and Cochrane databases (last search June 2016) was conducted to identify studies that reported randomized controlled trials (RCTs) comparing changes in blood glucose levels between patients receiving one of 12 antipsychotic drugs or a placebo for the treatment of schizophrenia or related disorders. The studies we searched were limited to those published in English. Two reviewers independently extracted data. The primary outcome of interest was changes in fasting glucose levels.. We included 47 studies with 114 relevant arms. Of the antipsychotic drugs, only olanzapine was associated with significantly increased glucose levels compared to a placebo (mean difference (MD) = 3.95, 95% confidence interval (CI) = 0.14 to 7.76). Moreover, olanzapine was associated with a significantly greater change in the glucose levels than ziprasidone (MD = 5.51, 95% CI = 1.62 to 9.39), lurasidone (MD = 5.58, 95% CI = 0.53 to 10.64) or risperidone (MD = 3.05, 95% CI = 0.87 to 5.22). Ziprasidone and lurasidone were associated with minimal glucose changes compared to the other antipsychotics.. Olanzapine was associated with a significantly greater change in blood glucose levels than ziprasidone, lurasidone, risperidone or placebo treatment. The application of a hierarchy of glucose metabolism-related side effects may help clinicians tailor the choice of antipsychotic drug to meet the needs of individual patients.

Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Humans; Insulin; Lurasidone Hydrochloride; Network Meta-Analysis; Olanzapine; Piperazines; Risperidone; Schizophrenia; Thiazoles

Insufficient treatment of psychosis often manifests as violent and aggressive behaviors that are dangerous to the patient and others, and that warrant treatment strategies which are not considered first-line, evidence-based practices. Such treatment strategies include both antipsychotic polypharmacy (simultaneous use of 2 antipsychotics) and high-dose antipsychotic monotherapy. Here we discuss the hypothesized neurobiological substrates of various types of violence and aggression, as well as providing arguments for the use of antipsychotic polypharmacy and high-dose monotherapy to target dysfunctional neurocircuitry in the subpopulation of patients that is treatment-resistant, violent, and aggressive. In this review, we focus primarily on the data supporting the use of second-generation, atypical antipsychotics both at high doses and in combination with other antipsychotics.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Brain; Clozapine; Dibenzocycloheptenes; Drug Therapy, Combination; Heterocyclic Compounds, 4 or More Rings; Humans; Impulsive Behavior; Isoxazoles; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Piperidines; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Receptors, Dopamine D2; Risperidone; Thiazoles; Violence

Treatment of bipolar depression is complicated by variable response and risk of switch to mania. Guidance is informed by the strength of evidence rather than by comparative data.. We performed a multiple-treatments meta-analysis of randomised, double-blind, controlled comparisons of 4-16 weeks in adults in bipolar depression. The primary efficacy outcome was effect size. The primary acceptability outcome was 'switch to mania'. Secondary outcomes were likelihood of response and withdrawals from trials.. Twenty-nine studies were included (8331 participants). Olanzapine + fluoxetine and olanzapine performed best on primary outcome measure being ranked highest for effect size. Switch to mania was least likely with ziprasidone and then quetiapine. Olanzapine + fluoxetine was also ranked the highest for response with lurasidone second, but olanzapine + fluoxetine and olanzapine had the optimal effect on response and withdrawal from treatment when the two parameters were considered together. Several treatments [monoamine oxidase inhibitors (MAOIs), ziprasidone, aripiprazole and risperidone] have limited or no therapeutic activity in bipolar depression.. Olanzapine + fluoxetine should be first-line treatment. Olanzapine, quetiapine, lurasidone, valproate and selective serotonin re-uptake inhibitors are also recommended. Tricyclic antidepressants and lithium are worthy of consideration but lamotrigine (high risk of switching, less robust efficacy) and MAOIs, ziprasidone, aripiprazole and risperidone (no evidence of efficacy) should not be used.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Depression; Dibenzothiazepines; Drug Therapy, Combination; Fluoxetine; Humans; Isoindoles; Lamotrigine; Lithium Compounds; Lurasidone Hydrochloride; Monoamine Oxidase Inhibitors; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Selective Serotonin Reuptake Inhibitors; Thiazoles; Treatment Outcome; Triazines; Valproic Acid

Patients with schizophrenia frequently switch between antipsychotics, underscoring the need to achieve and maintain important treatment outcomes such as health-related quality of life (HRQoL) following the switch. This analysis evaluated HRQoL changes among patients with schizophrenia switched from their current antipsychotic to lurasidone.. Stable but symptomatic outpatients with schizophrenia were switched from their current antipsychotic to lurasidone in a six-week, open-label trial. HRQoL was assessed using two validated patient-reported measures, the Personal Evaluation of Transitions in Treatment (PETiT) scale and the Short-Form 12 (SF-12). Total and domain scores (psychosocial function and adherence-related attitude) were assessed using the PETiT scale; patients' mental and physical component summary scores (MCS and PCS) were assessed using the SF-12. Changes in HRQoL from baseline to study endpoint were compared using ANCOVA, with baseline score, treatment, and pooled site as covariates. Changes were assessed among all patients and those switched from specific antipsychotics to lurasidone.. The analysis included 235 patients with data on the PETiT and SF-12 who had received ≥ 1 dose of lurasidone. Statistically significant improvements were observed from baseline to study endpoint on the PETiT total (mean change [SD]: 3.2 [8.5]) and psychosocial functioning (2.5 [6.9]) and adherence-related attitude (0.7 [2.6]) domain scores (all p ≤ 0.002). When examined by preswitch antipsychotic, significant improvements in PETiT total scores were observed in patients switched from quetiapine, risperidone, aripiprazole, and ziprasidone (all p < 0.03) but not olanzapine (p = 0.893). Improvements on the SF-12 MCS score were observed for all patients (mean change [SD]: 3.7 [11.5], p < 0.001) and for those switched from quetiapine or aripiprazole (both p < 0.03). The SF-12 PCS scores remained comparable to those at baseline in all patient groups.. These findings indicate that patients switching from other antipsychotics to lurasidone experienced statistically significant improvement of HRQoL, based on PETiT scores, within six weeks of treatment. Patient health status remained stable with respect to the SF-12 physical component and showed improvement on the mental component. Changes in HRQoL varied based on the antipsychotic used before switching to lurasidone.. NCT01143077.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Drug Substitution; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Olanzapine; Outpatients; Piperazines; Quality of Life; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Improving cognitive functioning in people with schizophrenia is a major treatment goal. In addition, interview-based measures have been developed to supplement performance-based assessments. However, few data are available regarding whether interview-based measures are sensitive to treatment-related changes.. Adult outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomized to 21 days of double-blind treatment with lurasidone 120 mg once daily (N=150) or ziprasidone 80 mg BID (N=151). A similar proportion of patients completed the study on lurasidone (67.5%) and ziprasidone (69.3%). Study participants were assessed with the majority of the tests from the MATRICS Consensus Cognitive Battery (MCCB) and an interview-based assessment of cognitive functioning, the Schizophrenia Cognition Rating Scale (SCoRS). SCoRS ratings were based on the interviewer's best judgment, after interviews with the patient and a caregiver when available. The study was conducted from April 2006 to January 2007.. There were no between-group treatment differences in performance on the MCCB or the SCoRS ratings. Lurasidone patients demonstrated significant within group-improvement from baseline on the MCCB composite score (p=0.026) and on the SCoRS (p<0.001), but ziprasidone patients did not improve on either the MCCB composite (p=0.254) or the SCoRS (p=0.185). At endpoint there was a statistical trend (p=0.058) for lurasidone to demonstrate greater improvement from baseline in SCoRS ratings. Improvements in interview-based aspects of cognition were not related to MCCB test changes, and had minimal correlations with changes in symptoms.. These data suggest that interview-based cognitive measures such as the SCoRS may be sensitive to changes after 3weeks of treatment in patients with schizophrenia. Lurasidone is being assessed further in ongoing clinical trials with additional outcome measures.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Interview, Psychological; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Thiazoles; Young Adult

Lurasidone is a new atypical antipsychotic agent with high affinity for D(2), 5-HT(2A) and 5-HT(7) receptors. The current study evaluated the safety and efficacy of lurasidone and ziprasidone in stable outpatients diagnosed with schizophrenia or schizoaffective disorder.. Adult outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder that was chronic (≥6 months duration) and stable were randomized to 21 days of double-blind treatment with a fixed dose of lurasidone 120 mg once daily (N=150) or ziprasidone 80 mg BID (N=151). Changes from baseline in efficacy measures were evaluated using mixed model for repeated measures (MMRM) analyses.. The proportion of patients who discontinued from the study was similar for lurasidone and ziprasidone (32.5% vs. 30.7%); the proportion who discontinued due to adverse events was similar (10.4% vs. 11.1%). Treatment with lurasidone and ziprasidone was associated with a small endpoint reduction in median weight (-0.65 kg vs. -0.35 kg) and median total cholesterol (-6.4 vs. -4.4 mg/dL); no endpoint change was observed in median triglycerides (0.0 vs. 0.0 mg/dL). There were no clinically significant changes in other laboratory or ECG parameters. Improvement was observed on an MMRM analysis of the PANSS total score for lurasidone and ziprasidone at Week 1 (-4.1 vs. -1.6; P=0.020), Week 2, (-6.1 vs. -3.6; P=0.074), and Week 3 (-6.3 vs. -4.5; P=0.229).. In this double-blind, fixed-dose comparison of lurasidone 120 mg and ziprasidone 160 mg, treatment with lurasidone was well-tolerated and safe, and was not associated with clinically significant changes from baseline in weight, metabolic parameters, or QTc interval. Study limitations include the relatively short trial duration and lack of placebo control.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Body Weight; Cholesterol; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Outpatients; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Thiazoles; Time Factors; Treatment Outcome; Triglycerides; Young Adult

While meta-analyses of clinical trials found that lurasidone and partial dopamine agonists (brexpiprazole and aripiprazole) were the antipsychotics less likely to cause QTc prolongation, and sertindole, amisulpride, and ziprasidone were the most frequently associated with this adverse drug reaction; no real-world studies have investigated this risk between the different antipsychotics.. Using data recorded from 1967 to 2019 in VigiBase®, the World Health Organization's Global Individual Case Safety Reports database, we performed disproportionality analysis to investigate the risk of reporting QT prolongation between 20 antipsychotics.. This large study in a real-world setting suggests that sertindole and ziprasidone were the antipsychotics drugs associated with the highest risk of QT prolongation reporting. Our results suggest that lurasidone is less associated with QT interval prolongation reports. Our study also suggests that antipsychotics with the higher hERG affinity are more associated with to QT prolongations reports.

Topics: Amisulpride; Antipsychotic Agents; Humans; Long QT Syndrome; Lurasidone Hydrochloride; Pharmacovigilance

Brexpiprazole is an oral atypical antipsychotic (OAA) for the treatment of schizophrenia (SCZ). This study compared all-cause and psychiatric inpatient hospitalization and medical costs in adult patients with SCZ newly treated with brexpiprazole versus other US Food and Drug Administration-approved OAAs in a real-world setting.. This retrospective cohort study analyzed data from: (1) the IBM MarketScan Commercial and Medicare Supplemental databases, and the MarketScan Multi-State Medicaid database; and (2) the de-identified Optum Clinformatics Datamart. Adult patients were identified if they had SCZ and initiated either brexpiprazole or another OAA during the study identification period (July 1, 2015, to September 30, 2016, for MarketScan Commercial and Medicare Supplemental and for Optum; July 1, 2015, to June 30, 2016, for MarketScan Multi-State Medicaid) and had ≥12 months of continuous enrollment before (baseline) and after (follow-up) the first treatment date. Linear regression analyses were performed to test associations between treatment groups (brexpiprazole vs another OAA) and costs (total and medical); negative binomial regression models were used to estimate number of hospitalizations per year, adjusting for baseline characteristics and medication adherence to index treatment during the 12-month follow-up.. The final study sample consisted of 6254 patients with SCZ: 176 initiated brexpiprazole; 391, ziprasidone; 453, paliperidone; 523, lurasidone; 786, aripiprazole; 1234, quetiapine; 1264, olanzapine; and 1427, risperidone. Controlling for baseline characteristics and medication adherence, the adjusted number of hospitalizations (both all-cause and psychiatric), all-cause total costs, and all-cause medical costs did not differ across groups. Brexpiprazole users had the lowest mean psychiatric costs among all OAA users ($12,013; 95% bootstrap CI, 7488-16,538). Compared with brexpiprazole users, paliperidone (incidence rate ratio [95% CI], 1.52 [1.05-2.19]; P = 0.027) and quetiapine (incidence rate ratio [95% CI], 1.47 [1.04-2.07]; P = 0.029) users had more psychiatric hospitalizations per year. Paliperidone had higher psychiatric costs than brexpiprazole (total, $32,066 [95% bootstrap CI, 28,779-35,353] vs $23,851 [18,907-28,795]; medical, $19,343 [16,294-22,392] vs $12,013 [7488-16,538]). Psychiatric medical costs were also $6744 higher in olanzapine users (95% bootstrap CI, 1694-11,795; P = 0.009) than in brexpiprazole users.. Patients with SCZ treated with brexpiprazole had fewer psychiatric hospitalizations and lower psychiatric costs than those treated with paliperidone. Differences in the number of all-cause hospitalizations and medical costs among treatments were not statistically significant. Although treatment decisions are driven by a number of factors (eg, clinical circumstances and drug costs), choice of OAA may affect health care costs.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Aripiprazole; Female; Health Care Costs; Hospitalization; Humans; Lurasidone Hydrochloride; Male; Medicaid; Medicare; Middle Aged; Olanzapine; Paliperidone Palmitate; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles; Thiophenes; United States

To compare adherence with lurasidone to other oral atypical antipsychotics among Medicaid and commercially insured patients with schizophrenia.. Administrative claims of patients with schizophrenia treated with atypical antipsychotics (lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone) from October 2010 to September 2011 were identified from MarketScan Commercial and Medicaid Databases, and were classified by the first (index) antipsychotic. Patients were 18-64 years, had insurance coverage 12 months pre- and 6 months post-index, and no pre-index use of the index drug.. Medication possession ratio (MPR), discontinuation rate, and mean time to discontinuation were assessed post-index. Pairwise comparisons (lurasidone versus each drug) were conducted using chi-square tests and Student's t-tests.. There were 146 Medicaid (mean age 43.5 years, 47.9% female) and 63 commercial (mean age 40.0 years, 42.9% female) patients treated with lurasidone. In the Medicaid population, the MPR for patients treated with lurasidone was 0.60, versus 0.41-0.48 for patients treated with other antipsychotics (all p < .05). Patients treated with lurasidone exhibited a lower discontinuation rate compared to patients treated with all other antipsychotics (49.3% versus 62.3%-68.3%, all p < .05). The mean time to discontinuation with lurasidone was significantly longer than with ziprasidone (p < .05). In the commercial population, the MPR for patients treated with lurasidone (0.61) was higher compared to patients treated with quetiapine (0.44) and ziprasidone (0.43) (both p < .05). The discontinuation rate (44.4%) was lower for patients treated with lurasidone compared to patients treated with all other antipsychotics except risperidone (p < .05). The mean time to discontinuation was longer for lurasidone than with other antipsychotics.. In Medicaid and commercial populations, patients treated with lurasidone demonstrated greater adherence compared to patients treated with other atypical antipsychotics. Limitations of using administrative claims data include potential errors or inconsistencies in coding, and lack of complete clinical information.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Female; Humans; Insurance Claim Review; Lurasidone Hydrochloride; Male; Medicaid; Medication Adherence; Middle Aged; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; United States

A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed for the determination of an atypical antipsychotic drug, lurasidone, in rat plasma. The method involves the addition of acetonitrile and ziprasidone (internal standard) solution to plasma samples, followed by centrifugation. An aliquot of the supernatant was diluted with water and directly injected into the LC/MS/MS system. The separations were performed on a column packed with octadecylsilica (5 μm, 2.0 × 50 mm) with 0.1% formic acid and 0.1% formic acid in acetonitrile as mobile phase and the detection was performed using tandem mass spectrometry by multiple-reaction monitoring via an electrospray ionization source. The standard curve was linear (r = 0.9982) over the concentration range 0.002-1 μg/mL. The intra- and inter-assay precisions were 1.7 and 8.6%, respectively. The accuracy range was from 90.3 to 101.8%. The lower limit of quantification was 2.0 ng/mL using 50 μL of rat plasma sample. The developed analytical method was successfully applied to the pharmacokinetic study of lurasidone in rats.

Topics: Acetonitriles; Animals; Antipsychotic Agents; Chromatography, High Pressure Liquid; Isoindoles; Linear Models; Lurasidone Hydrochloride; Male; Piperazines; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry; Thiazoles

This study aimed to characterise the pharmacokinetics of lurasidone, a new atypical anti-psychotic drug, in rats after intravenous and oral administration at dose range 0.5-2.5 and 2.5-10 mg/kg, respectively. Moreover, tissue distribution, liver microsomal stability and plasma protein binding were estimated. After intravenous injection, systemic clearance, steady-state volumes of distribution and half-life remained unaltered as a function of dose with values in the range 22.1-27.0 mL/min/kg, 2,380-2,850 mL/kg and 229-267 min, respectively. Following oral administration, absolute oral bioavailability was not dose dependent with approximately 23%. The recoveries of lurasidone in urine and bile were 0.286% and 0.0606%, respectively. Lurasidone was primarily distributed to nine tissues (brain, liver, kidneys, heart, spleen, lungs, gut, muscle and adipose) and tissue-to-plasma ratios of lurasidone were ranged from 1.06 (brain) to 9.16 (adipose). Further, lurasidone was unstable in rat liver microsome and the plasma protein binding of lurasidone was concentration independent with approximately 99.6%. In conclusion, lurasidone showed dose-independent pharmacokinetics at an intravenous dose of 0.5-2.5 mg/kg and an oral dose of 2.5-10 mg/kg. Lurasidone was primarily distributed to nine tissues and appeared to be primarily eliminated by its metabolism.

Topics: Administration, Oral; Animals; Antipsychotic Agents; Injections, Intravenous; Isoindoles; Lurasidone Hydrochloride; Male; Piperazines; Rats; Rats, Sprague-Dawley; Reference Standards; Thiazoles