Objective: To determine the electrophysiological effects and related mechanisms of late sodium current inhibitors on hearts with short QT intervals. Methods: The electrophysiological study was performed on isolated Langendorff perfused rabbit hearts. A total of 80 New Zealand White rabbits were used and 34 hearts without drug treatment were defined as control group A, these hearts were then treated with I_KATP opener pinacidil, defined as pinacidil group A. Then, 27 hearts from pinacidil group A were selected to receive combined perfusion with sodium channel inhibitors or quinidine, a traditional drug used to treat short QT syndrome, including ranolazine combined group (n=9), mexiletine combined group (n=9), and quinidine combined group (n=9). Nineteen out of the remaining 46 New Zealand rabbits were selected as control group B (no drug treatments, n=19), and then treated with pinacidil, defined as pinacidil group B (n=19). The remaining 27 rabbits were treated with sodium inhibitors or quinidine alone, including ranolazine alone group (n=9), mexiletine alone group (n=9), and quinidine alone group (n=9). Electrocardiogram (ECG) physiological parameters of control group A and pinacidil group A were collected. In control group B and pinacidil group B, programmed electrical stimulation was used to induce ventricular arrhythmias and ECG was collected. ECG physiological parameters and ventricular arrhythmia status of various groups were analyzed. The concentrations of pinacidil, ranolazine, mexiletine and quinidine used in this study were 30, 10, 30 and 1 μmol/L, respectively. Results: Compared with control group A, the QT interval, 90% of the repolarization in epicardial and endocardial monophasic action potential duration (MAPD₉₀-Epi, MAPD₉₀-Endo) was shortened, the transmural dispersion of repolarization (TDR) was increased, and the effective refractor period (ERP) and post-repolarization refractoriness (PRR) were reduced in pinacidil group A (all P<0.05). Compared with the pinacidil group A, MAPD₉₀-Epi, MAPD₉₀-Endo, QT interval changes were reversed in quinidine combined group and mexiletine combined group (all P<0.05), but not in ranolazine combined group. All these three drugs reversed the pinacidil-induced increases of TDR and the decreases of ERP and PRR. The induced ventricular arrhythmia rate was 0 in control group B, and increased to 10/19 (χ²=13.6, P<0.05) in pinacidil group B during programmed electrical stimulation. Compared with the pinacidil group B, incidences of ventricular arrhythmia decreased to 11% (1/9), 11% (1/9) and 0 (0/9) (χ²=4.5, 4.5, 7.4, P<0.05) respectively in ranolazine group, mexiletine group and quinidine group. Conclusions: Inhibition of late sodium current does not increase but even decreases the risk of malignant arrhythmia in hearts with a shortened QT interval. The antiarrhythmic mechanism might be associated with the reversal of the increase of TDR and the decrease of refractoriness (including both ERP and PRR) of hearts with shortened QT interval.
Rabbits ; Animals ; Quinidine/therapeutic use* ; Mexiletine/therapeutic use* ; Pinacidil/therapeutic use* ; Sodium ; Ranolazine/therapeutic use* ; Electrophysiologic Techniques, Cardiac ; Arrhythmias, Cardiac/drug therapy*

Anti-Arrhythmia Agents ; Brugada Syndrome/complications* ; Bundle-Branch Block/complications* ; Electrocardiography ; Humans ; Quinidine ; Ventricular Fibrillation

Nuedexta (dextromethorphan and quinidine) is an Food and Drug Administration approved medication for pseudobulbar affect. Interestingly, this drug was recently reported to improve speech, swallowing, and the ability to handle oral secretions along with emotional lability in amyotrophic lateral sclerosis (ALS) patients with bulbar symptoms. We report a Korean ALS patient whose bulbar function improved after administering Nuedexta for 6 months, extending therapeutic choice of approach in treating ALS patients.
Amyotrophic Lateral Sclerosis ; Deglutition ; Dextromethorphan ; Humans ; Quinidine ; United States Food and Drug Administration

BACKGROUND/AIMS: Nutrient-induced gut hormone release (eg, cholecystokinin [CCK]) and the modulation of gut motility (particularly pyloric stimulation) contribute to the regulation of acute energy intake. Non-caloric bitter compounds, including quinine, have recently been shown in cell-line and animal studies to stimulate the release of gastrointestinal hormones by activating bitter taste receptors expressed throughout the gastrointestinal tract, and thus, may potentially suppress energy intake without providing additional calories. This study aims to evaluate the effects of intraduodenally administered quinine on antropyloroduodenal pressures, plasma CCK and energy intake. METHODS: Fourteen healthy, lean men (25 ± 5 years; BMI: 22.5 ± 2.0 kg/m²) received on 4 separate occasions, in randomized, double-blind fashion, 60-minute intraduodenal infusions of quinine hydrochloride at doses totaling 37.5 mg (“Q37.5”), 75 mg (“Q75”) or 225 mg (“Q225”), or control (all 300 mOsmol). Antropyloroduodenal pressures (high-resolution manometry), plasma CCK (radioimmunoassay), and appetite perceptions/gastrointestinal symptoms (visual analog questionnaires) were measured. Ad libitum energy intake (buffet-meal) was quantified immediately post-infusion. Oral quinine taste-thresholds were assessed on a separate occasion using 3-alternative forced-choice procedure. RESULTS: All participants detected quinine orally (detection-threshold: 0.19 ± 0.07 mmol/L). Intraduodenal quinine did not affect antral, pyloric or duodenal pressures, plasma CCK (pmol/L [peak]; control: 3.6 ± 0.4, Q37.5: 3.6 ± 0.4, Q75: 3.7 ± 0.3, Q225: 3.9 ± 0.4), appetite perceptions, gastrointestinal symptoms or energy intake (kcal; control: 1088 ± 90, Q37.5: 1057 ± 69, Q75: 1029 ±70, Q225: 1077 ± 88). CONCLUSION: Quinine, administered intraduodenally over 60 minutes, even at moderately high doses, but low infusion rates, does not modulate appetite-related gastrointestinal functions or energy intake.
Animals ; Appetite ; Cholecystokinin ; Energy Intake ; Gastrointestinal Hormones ; Gastrointestinal Tract ; Humans ; Male ; Plasma ; Pylorus ; Quinine

Solifenacin is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms. Solifenacin tartrate is a newly developed salt formulation of solifenacin. This study compared the pharmacokinetic and safety properties after single-dose administration of solifenacin tartrate (test formulation) and solifenacin succinate (reference formulation) in healthy male volunteers. A total of 36 subjects were enrolled in this randomized, open-label, single-dose, two-way crossover study. During each treatment period, subjects received the test formulation or reference formulation. Plasma samples were collected at pre-dose and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48 and 72 hours post-dose. Safety was assessed by adverse events, physical examinations, laboratory assessments, 12-lead electrocardiograms, and vital signs. Thirty-three subjects completed the study and were included in the pharmacokinetic analysis. The mean (standard deviation) values of AUC(last) for the test and reference formulations were 486.98 (138.47) and 469.07 (128.29) h·ng/mL, respectively. The mean (standard deviation) values of C(max) for the test and reference formulations were 14.66 (3.85) and 14.10 (3.37) ng/mL, respectively. The 90% confidence intervals for AUC(last) and C(max) were 0.9702 to 1.1097 and 0.9779 to 1.0993, respectively. All adverse events were mild or moderate, and there were no serious adverse events. The pharmacokinetic properties of solifenacin tartrate were similar to those of solifenacin succinate and met the acceptance criteria for bioequivalence. Both formulations were safe, and no significant difference was observed in the safety assessments of the formulations.
Cross-Over Studies ; Electrocardiography ; Humans ; Male ; Pharmacokinetics ; Physical Examination ; Plasma ; Solifenacin Succinate ; Therapeutic Equivalency ; Urinary Bladder, Overactive ; Vital Signs ; Volunteers

PURPOSE: To compare the clinical efficacy of anticholinergics for managing diabetes mellitus-associated overactive bladder (DM OAB) versus idiopathic overactive bladder (OAB) in Korean women. METHODS: We conducted a multicenter, prospective, parallel-group, open-label, 12-week study. Women (20–65 years old) with OAB symptoms for over 3 months were assigned to the DM OAB and idiopathic OAB groups. Changes in the Overactive Bladder Symptom Score (OABSS), urgency, urinary urgency incontinence, nocturia, daytime frequency according to a voiding diary, uroflowmetry, and postvoid residual urine volume (PVR) at the first visit (V1), week 4 (V2), and week 12 (V3) were compared. RESULTS: No significant difference was found between the baseline patient characteristics of the DM OAB and idiopathic OAB groups. Treatment with solifenacin was associated with improvements in urgency, urinary urgency incontinence, nocturia, frequency according to a voiding diary, and the total OABSS between V1 and V2 and between V1 and V3. Moreover, a significant improvement in urgency and urge incontinence was found between V2 and V3 in the DM OAB group. However, no significant changes were found in any other parameters. There were no significant differences between the DM OAB group and the idiopathic OAB group except for urgency and urge incontinence at V2 (3.71 vs. 2.28 and 0.47 vs. 0.32, respectively). CONCLUSIONS: The patients who received solifenacin demonstrated improved urgency, urinary urgency incontinence, nocturia, frequency according to a voiding diary, and total OABSS. Management with solifenacin was equally effective for both DM-related OAB and idiopathic OAB.
Cholinergic Antagonists ; Diabetes Mellitus ; Female ; Humans ; Nocturia ; Prospective Studies* ; Solifenacin Succinate* ; Treatment Outcome* ; Urinary Bladder, Overactive* ; Urinary Incontinence, Urge

PURPOSE: The aim of this study was to investigate the safety and the effects of elevated doses of solifenacin and trospium on cognitive function and health-related quality of life (HRQoL) in elderly women receiving treatment for urinary incontinence. METHODS: The study included 312 women aged 60–83 years (mean age, 69.4 years). All participants had scored at least 24 points on the Mini-Mental State Examination (MMSE) scale, and all of them had been diagnosed with urge urinary incontinence (UUI) or mixed urinary incontinence (MUI). The women were randomly assigned to 3 groups: group A, individuals who were simultaneously administered solifenacin at a high dosage of 20 mg per day and trospium at a high dosage of 60 mg per day; group B, persons taking solifenacin and trospium at the usual dosage of 10 and 30 mg per day, respectively; and group C, persons who received a placebo. Participants’ cognitive status was assessed by the MMSE, Controlled Oral Word Association Test, Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale III, Colour Trails Test, and California Verbal Learning Test scales. The HRQoL assessment was performed using the Medical Outcomes Study 36-Item Health Survey. RESULTS: The cognitive function parameters did not differ at the start and end of the study across the groups (P>0.05). Additionally, the cognitive function parameters did not differ significantly within each group between the start and end of the study (P>0.05). The values of most HRQoL parameters regarding the functional state of the lower urinary tract (LUT) after the termination of treatment significantly improved in groups A and B (P < 0.05). A significant correlation between cognitive status and HRQoL or LUT parameters was absent (r < 0.3), while the correlations between HRQoL and LUT parameters were r=0.31–0.83, P < 0.05. CONCLUSIONS: The use of elevated doses of solifenacin and trospium did not increase the risk of cognitive impairment in women with UUI and MUI. The combination of solifenacin and trospium at a double dosage may be recommended to elderly women with treatment-resistant symptoms of UUI and MUI. However, the safety of combining antimuscarinic drugs in women with an increased volume of residual urine requires further study.
Adult ; Aged ; California ; Cognition Disorders ; Cognition* ; Female ; Health Surveys ; Humans ; Intelligence ; Memory ; Muscarinic Antagonists ; Quality of Life* ; Solifenacin Succinate* ; Urinary Incontinence* ; Urinary Tract ; Verbal Learning ; Weights and Measures ; Word Association Tests

PURPOSE: We performed a meta-analysis to evaluate the efficacy and safety of mirabegron add-on therapy to solifenacin for patients with overactive bladder (OAB). METHODS: We conducted a systematic literature review to identify all randomized, double-blind, controlled trials (RCTs) of this combination (mirabegron and solifenacin) for OAB. Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched. A manual search was also performed to investigate relevant references from the retrieved studies. RESULTS: Four publications describing 5 RCTs that compared combination therapy with solifenacin, including a total of 3,309 patients, were analyzed. The mean number of micturitions per 24 hours (mean difference [MD], -0.45; 95% confidence interval [CI], -0.65 to -0.26; P < 0.00001), number of episodes of incontinence per 24 hours (MD, -0.71; 95% CI, -0.14 to -0.02; P=0.04), volume voided per micturition, and number of urgency episodes per 24 hours demonstrated that combination therapy was more effective than solifenacin therapy alone. Safety assessments, including common treatment-emergent adverse events (odds ratio, 1.09; 95% CI, 0.95–1.27; P=0.23) and discontinuations due to adverse events (P=0.30), demonstrated that the combination therapy was well tolerated. CONCLUSIONS: This meta-analysis suggests that mirabegron therapy as an add-on to solifenacin provides a satisfactory therapeutic effect for OAB symptoms with a low occurrence of side effects.
Humans ; Solifenacin Succinate* ; Urinary Bladder, Overactive* ; Urination

We compared changes in nocturia and sleep-related parameters between daytime and nighttime solifenacin dosing in patents with overactive bladder (OAB) and nocturia. We comparatively analyzed the data of a 12-week prospective, open-label, multicenter, randomized study. All 127 patients who presented to 5 centers in Korea for the treatment of OAB with nocturia between January 2011 and December 2013 were enrolled in this study. The patients were divided into 2 groups by medication timing: group 1, daytime (n = 62); and group 2, nighttime (n = 65). The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and Athens Insomnia Scale (AIS) were used to assess OAB symptoms and sleep quality. We evaluated the parameter changes before and 12 weeks after daytime or nighttime solifenacin administration. Baseline data, which included sex, age, body mass index (BMI), total AIS, IPSS, and OABSS, did not differ between the 2 groups. Total IPSS, OABSS, and total AIS significantly improved after solifenacin administration regardless of timing (P < 0.001). After solifenacin administration, the number of nocturia episodes decreased in the group 1 and 2 (P < 0.001). There were no significant intergroup differences in changes in AIS, IPSS, OABSS, and number of nocturia episodes 12 weeks after solifenacin administration. Treating OAB with solifenacin may improve nocturia and sleep quality, but advantages did not differ significantly by medication timing.
Body Mass Index ; Humans ; Korea ; Nocturia* ; Prospective Studies ; Prostate ; Sleep Initiation and Maintenance Disorders ; Solifenacin Succinate* ; Urinary Bladder, Overactive*

Blackwater fever is a serious clinical syndrome manifested by acute intravascular hemolysis, fever, and the passage of black or red urine, which is classically associated with falciparum malaria and irregular administration of quinine. In Korea, Plasmodium vivax is the only endemic malaria circulating; a number of imported cases of falciparum malaria have been reported in patients following return from international travel to a malaria endemic area. Therefore, it is important for health care professionals including pediatricians to be aware of the falciparum malaria and its clinical courses. Herein, we report a case of a 14-year-old girl with severe falciparum malaria that was complicated by blackwater fever.
Adolescent ; Blackwater Fever* ; Child* ; Delivery of Health Care ; Female ; Fever ; Hemolysis ; Humans ; Korea ; Malaria* ; Malaria, Falciparum ; Plasmodium vivax ; Quinine