No abstract available.
Arthritis, Rheumatoid ; Isoxazoles

No abstract available.
Drug Hypersensitivity ; Isoxazoles

OBJECTIVE: Schizophrenia is a chronic and persistent mental illness and requires continuous treatment. Nevertheless, a majority of schizophrenia subjects show non-adherence to oral antipsychotics due to many factors including a lack of insight and a decline in their cognitive function. Medication non-adherence is associated with an increase in relapse and hospitalization and incurs a heavy burden not only to subjects and caregivers, but also to society. Treatment with antipsychotic long acting injection can maintain a consistent plasma drug concentration and has been shown to prevent relapse and re-hospitalization. This study aims to assess the cost-effectiveness of paliperidone palmitate long acting injection (PLAI) compared with atypical oral antipsychotics (risperidone, olanzapine, aripiprazole and paliperidone) in schizophrenia subjects who are non-adherent to oral atypical antipsychotics. METHODS: A decision-tree model was constructed to compare the clinical and economic outcomes of PLAI and oral comparator over 1 year in schizophrenia subjects who are non-adherent to oral atypical antipsychotics. Clinical data such as relapse rate, extra pyramidal symptoms (EPS) rate, suicide rate and non-adherence rate were obtained from published literature. Utility values for each schizophrenia health state were calculated based on an Australian study to measure the utility values for schizophrenia patients. Direct medical cost data were obtained from domestic literature. Sensitivity analyses were performed on major variables. RESULTS: Based on model estimates, PLAI can increase quality-adjusted life years (QALY) per patient by 0.39 and is associated with a 2.93-fold lower probability of relapse compared with the weighted average of the oral treatments (0.2204 vs 0.6462). The total annual medical costs per patient (including medication, inpatient and outpatient cost) were 4.51 million Korean Won for PLAI, and 5.19 million Korean Won for the weighted average of oral atypical antipsychotics, leading to a cost reduction of 0.68 million Korean Won with PLAI. CONCLUSION: With lower total medical cost and improved treatment outcomes compared to oral treatments, PLAI was assessed to be a dominant treatment option for schizophrenia patients who are non-adherent to oral atypical antipsychotics.
Antipsychotic Agents ; Benzodiazepines ; Caregivers ; Hospitalization ; Humans ; Inpatients ; Isoxazoles ; Medication Adherence ; Outpatients ; Palmitates ; Piperazines ; Plasma ; Pyrimidines ; Quality-Adjusted Life Years ; Quinolones ; Recurrence ; Republic of Korea ; Schizophrenia ; Suicide ; Aripiprazole ; Paliperidone Palmitate

To develop a parent-metabolite pharmacokinetic model for risperidone (RIP) and its major active metabolite (9-hydroxyrisperidone) and investigate their pharmacokinetics characteristics in healthy male volunteers, twenty-two healthy volunteers were orally given a single dose of 2 mg RIP. Plasma samples were collected in the period of 96 hours and concentrations of RIP and 9-hydroxyrisperidone were measured by a validated HPLC/MS method. CYP2D6 phenotypes were identified by the T1/2 of RIP and 9-hydroxyrisperidone according to the literature. Model structure identifiability analysis was performed by the similarity transformation approach to investigate whether the unknown parameters of the proposed model could be estimated from the designed experiment. Pharmacokinetics parameters were estimated using weighted least squares method, and the final pharmacokinetics model were tested and evaluated by Monte Carlo simulation. Eighteen volunteers were phenotyped as extensive metabolizers (EM) and four volunteers were identified as intermediate metabolizers (IM). The final model included central and peripheral compartment for both parent (RIP) and metabolite (9-hydroxyrisperidone) respectively. Model structure identifiability analysis indicated that the proposed model was local identifiable. However, if the ratio of RIP converted to 9-hydroxyrisperidone was assumed to be 32% in EM, and 22% in IM, the model could be globally identifiable. The predicted time-concentration curve and AUC(0-t), C(max), T(max) of RIP and 9-hydroxyrisperidone estimated by the established model were in agreement with the observations and noncompartment analysis. Rate constant of RIP conversion to 9-hydroxyrisperidone was (0.12 +/- 0.08) h(-1) and (0.014 +/- 0.007) h(-1) for EM and IM, respectively. Elimination rate constants of RIP were (0.25 +/- 0.18) and (0.05 +/- 0.23) h(-1) for EM and IM, respectively. Model validation result showed that all parameters derived from the concentration data fitted well with the theoretical value, with mean prediction error of most PK parameter within +/- 15%. The established model well defined the disposition of RIP and 9-hydroxyrisperidone simultaneously and showed large inter-individual pharmacokinetics variation in different CYP2D6 phenotype. The model also provide a useful approach to characterize pharmacokinetics of other parent-metabolite drugs.
Adult ; Cytochrome P-450 CYP2D6 ; physiology ; Humans ; Isoxazoles ; pharmacokinetics ; Male ; Models, Biological ; Monte Carlo Method ; Paliperidone Palmitate ; Pyrimidines ; pharmacokinetics ; Risperidone ; pharmacokinetics

BACKGROUND AND PURPOSE: To evaluate changes in cortical excitability induced by zonisamide (ZNS) in focal epilepsy patients. METHODS: Twenty-four drug-nasmall yi, Ukrainianve focal epilepsy patients (15 males; overall mean age 29.8 years) were enrolled. The transcranial magnetic stimulation parameters obtained using two Magstim 200 stimulators were the resting motor threshold, amplitude of the motor-evoked potential (MEP), cortical silent period, short intracortical inhibition, and intracortical facilitation. These five transcranial magnetic stimulation parameters were measured before and after ZNS, and the findings were compared. RESULTS: All 24 patients were treated with ZNS monotherapy (200-300 mg/day) for 8-12 weeks. After ZNS, MEP amplitudes decreased (-36.9%) significantly in epileptic hemispheres (paired t-test with Bonferroni's correction for multiple comparisons, p<0.05), whereas the mean resting motor threshold, cortical silent period, short intracortical inhibition, and intracortical facilitation were unchanged (p>0.05). ZNS did not affect cortical excitability in nonepileptic hemispheres. CONCLUSIONS: These findings suggest that ZNS decreases cortical excitability only in the epileptic hemispheres of focal epilepsy patients. MEP amplitudes may be useful for evaluating ZNS-induced changes in cortical excitability.
Epilepsies, Partial ; Humans ; Isoxazoles ; Transcranial Magnetic Stimulation

BACKGROUND AND PURPOSE: To evaluate changes in cortical excitability induced by zonisamide (ZNS) in focal epilepsy patients. METHODS: Twenty-four drug-nasmall yi, Ukrainianve focal epilepsy patients (15 males; overall mean age 29.8 years) were enrolled. The transcranial magnetic stimulation parameters obtained using two Magstim 200 stimulators were the resting motor threshold, amplitude of the motor-evoked potential (MEP), cortical silent period, short intracortical inhibition, and intracortical facilitation. These five transcranial magnetic stimulation parameters were measured before and after ZNS, and the findings were compared. RESULTS: All 24 patients were treated with ZNS monotherapy (200-300 mg/day) for 8-12 weeks. After ZNS, MEP amplitudes decreased (-36.9%) significantly in epileptic hemispheres (paired t-test with Bonferroni's correction for multiple comparisons, p<0.05), whereas the mean resting motor threshold, cortical silent period, short intracortical inhibition, and intracortical facilitation were unchanged (p>0.05). ZNS did not affect cortical excitability in nonepileptic hemispheres. CONCLUSIONS: These findings suggest that ZNS decreases cortical excitability only in the epileptic hemispheres of focal epilepsy patients. MEP amplitudes may be useful for evaluating ZNS-induced changes in cortical excitability.
Epilepsies, Partial ; Humans ; Isoxazoles ; Transcranial Magnetic Stimulation

Valproate is widely used because of broad spectrum of action, but it can produce an encephalopathy resulting from hyperammonemia even at the therapeutic range of valproate and is called as valproate-induced encephalopathy (VHE). Delay in recognition of VHE can result in the development of potentially life-threatening complications. Fortunately, it is reversible with discontinuing valproate. A 65-year-old man became progressively lethargic with impaired gait and poor cognitive function while taking valproate as alternative to zonisamide. Routine investigations of admission profiles were performed but revealed no abnormalities. Next, we checked serum ammonia level to identify other possible causes and detected hyperammonemia despite the therapeutic range of valproate in the absence of any abnormalities in liver enzymes. On cessation of valproate, he has achieved dramatic clinical improvement including the reversal of hyperammonemia. We confirmed the diagnosis of VHE. This emphasizes the importance of rapid diagnosis and proper management of VHE in order to prevent the neurological damage and minimize complications.
Aged ; Ammonia ; Gait ; Humans ; Hyperammonemia ; Isoxazoles ; Liver ; Valproic Acid

Zonisamide (ZNS) has been proven as a safe, effective, and well-tolerated antiepileptic drug. We report an epilepsy patient who had a severe, dose-dependent, memory deficit after ZNS administration. A 65-year-old man visited our epilepsy clinic due to the occurrence of nocturnal convulsions. Despite the absence of seizures, he developed a severe impairment of verbal and visual memory functions after the increment of ZNS dosage from 200 mg/day to 300 mg/day. We substituted 1,000 mg/day valproic acid for ZNS. His cognitive performances were returned to original levels.
Aged ; Epilepsy ; Humans ; Isoxazoles ; Memory ; Memory Disorders ; Seizures ; Valproic Acid

OBJECTIVES: We investigated the tolerability, safety, and treatment response to flexible-dose paliperidone ER in patients with non-acute schizophrenia in whom previous antipsychotic drugs were ineffective. METHODS: This 24-week interim analysis of the 48-week multicenter, prospective, open-label study assessed effectiveness using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia-Severity (CGI-SCH-S) Scale, Personal and Social Performance (PSP) and Drug Attitude Inventory (DAI). Safety and tolerability were assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). RESULTS: Effectiveness was assessed in 169 patients. Significant improvement in the PANSS total score was observed by week-1 and continued until week-24. The response rate was 33%. The CGI-SCH-S and PSP total scores significantly improved during 24 weeks ; however, no change occurred in the total DAI. Fifty-nine percent of patients reported adverse events, of which extrapyramidal symptoms were the most frequent (19.0%). The DIEPSS and LUNSERS scores were improved after 24 week. CONCLUSIONS: Switching to the flexible-dose paliperidone ER from an ineffective antipsychotic drug was safe, tolerable, and showed a good treatment response in Korean patients with schizophrenia.
Antipsychotic Agents ; Humans ; Isoxazoles ; Prospective Studies ; Pyrimidines ; Schizophrenia

The objective of the study is to monitor on a wide population base the safety and efficacy of zonisamide in patients with partial, generalized, and combined seizures. This is an open label, descriptive, post-marketing surveillance preliminary report that includes the data obtained from October 2008 to May 2010 of a four-year study. The study included 516 patients allocated to either zonisamide monotherapy or zonisamide add-on therapy, with efficacy and safety assessed monthly for three months. For adult patients, a maximum oral dose of 600 mg per day was allowed while a maximum dose of 12 mg/kg/day of zonisamide was allowed for pediatric patients. Efficacy measures were the proportion of responders and percentage change in seizure frequency from baseline. 321 of the 516 patients were included in the efficacy analysis. The responder rates were 53.27%, 80.37%, and 92.52% after the 1st month, 2nd month, and 3rd month of treatment respectively. The use of zonisamide led to seizure-reduction rates of 45.74%, 68.43%, & 82.85% during the 1st, 2nd, & 3rd month of use respectively. Safety analysis was done on all the 516 subjects. Adverse events were mostly mild and observed in 6.78% of patients. No serious adverse events were encountered. 7 subjects (1.4%) discontinued taking zonisamide because of increased seizure frequency in 4 patients, and 1 patient each due to absence of effect on seizure-control, rashes, and thrombocytopenia. All the rest continued taking zonisamide.

Human ; Male ; Female ; Seizures ; Zonisamide ; Isoxazoles ; Exanthema ; Marketing ; Thrombocytopenia ; Epilepsy