Clinical characteristics and treatment outcomes of patients with Brugada syndrome in northeastern Thailand

<p><b>INTRODUCTION</b>Brugada syndrome (BrS) is a common genetic cause of sudden cardiac arrest (SCA) due to polymorphic ventricular tachycardia and ventricular fibrillation. The current recommended therapy for high-risk BrS patients is the use of an implantable cardioverter defibrillator (ICD). The present study aimed to report the clinical characteristics and treatment outcomes of BrS patients in northeastern Thailand.</p><p><b>METHODS</b>Patients who were diagnosed with BrS or had a Brugada electrocardiogram (ECG) between 2005 and 2012 at Khon Kaen University's hospitals were enrolled in the present study. Patients' clinical characteristics, ECG type, laboratory results and treatment were reviewed.</p><p><b>RESULTS</b>A total of 90 eligible patients were enrolled. Of these, 79 (87.8%) patients were symptomatic--65 (82.3%) had documented SCA and 14 (17.7%) had unexplained syncope. The remaining 11 (12.2%) patients were asymptomatic with Brugada ECG. A majority of the patients enrolled were born in northeastern Thailand. The mean age of the symptomatic patients was 44.49 ± 8.55 years. Among the symptomatic patients, a majority were male (n = 77, 97.5%) and 23 (29.1%) patients had a family history of SCA. Almost all BrS patients who were symptomatic (96.2%) received ICD treatment for secondary prevention. The number of patients who received appropriate ICD therapy was 4.2 times of those who received inappropriate shocks. Only 3 (3.8%) symptomatic BrS patients refused ICD treatment.</p><p><b>CONCLUSION</b>Clinical characteristics did not distinguish between symptomatic BrS patients and asymptomatic patients with Brugada ECGs. The clinical characteristics and treatment outcomes for the symptomatic BrS patients with SCA and unexplained syncope were similar. Among the BrS patients implanted with secondary prevention ICD in Northeastern Thailand, nearly one-third had received appropriate ICD therapy, far exceeding the incidence of device-related complications and inappropriate therapy.</p>

Comparison of Italic cytoxicity of generic paclitaxel and irinotecan formulations with their reference formulations on seven human intrahepatic cholangiocarcinoma cell lines

Background: Several chemotherapies have now been introduced for the treatment of cholangiocarcinoma (CCA).  Although it has previously been reported that two new chemotherapeutic agents, paclitaxel and irinotecan, showed strong cytotoxic effect to human CCA cell lines the treatment cost currently using reference formulations of these two drugs are very expensive.  To date, the generic drugs for both paclitaxel and irinotecan are now commercially available in Thailand with relatively low price compared to reference formulations.  However, the study demonstrating the efficacy of the innovator and generic formulation of these two agents has never been reported.Objective: To determine and compare the cytotoxic activity of generic paclitaxel and irinotecan formulations with the reference formulations on seven human intrahepatic CCA cell lines.Design: In vitro studySetting: Faculty of Medicine, Khon Kaen UniversityMaterial and Method: Cytotoxic activitiy of chemotherapeutic agent on CCA cellines was determined by sulforhodamine B (SRB) assay.  The IC50 value expressed as the concentration of drug that caused a 50% growth inhibition comparing with no drug treated control.  The cytotoxic activity of the generic formulation was compared to the reference formulation using Student’s unpaired t-test.Results: Paclitaxel exhibited strong potency towards most CCA cell lines with IC50 values ranging from 0.001-1.40 mM whereas irinotecan showed IC50 values ranging varied from 0.02 to 69 mM. KKU-M055 was the most sensitive cell line to paclitaxel and KKU-OCA17 showed the highest sensitivity to irinotecan whereas KKU-M156 was the least sensitive cell line to both drugs. IC50 values of the generic product (IntaxelÒ, Dabur, India) and reference product (TaxolÒ, Bristol-Myers Squibb, USA) formulations were not significantly different (P \> 0.05).  Similary, the cytotoxicity of the generic formulation of irinotecan (IrinotelÒ, Dabur, India) was not statistically significant different from the reference formulation (CamptoÒ, Aventis Pharma, UK).Conclusion: The cytotoxic activity of paclitaxel towards six CCA cell lines was more potent than irinotecan except for KKU-OCA17.  No different in the IC50 values of the generic and reference formulations of paclitaxel and irinotecan against seven CCA lines suggest that the in vitro efficacy of generic and reference formulations of these two drugs are very similar.  

Determination of Growth Inhibitory Effect of Gemcitabine on Human Intrahepatic Cholangiocarcinoma Cell lines and Comparison of its Inhibition Between the Generic and Reference Formulation

Background and Objective: Gemcitabine is one of the most popular drug-of-choices that is currently used for the treatment of cholangiocarcinoma (CCA).\  However, the study revealing the inhibitory effect of this agent in the series of CCA cell lines established from Thai patients has not been reported. We aim to determine and compare the growth inhibitory effect of generic gemcitabine formulation with the reference formulation on CCA cell lines.Methods: Seven CCA cell lines established in Srinagarind Hospital, Khon Kaen University were used. A cell growth inhibition by gemcitabine was determined by sulforhodamine B.\  The IC50 value was expressed as the concentration of drug that caused a 50% growth inhibition comparing with untreated control.\  The IC50 values of those two formulations were compared using independent t-test.Results: Growths of KKU-M055, KKU-OCA17 and KKU-M139 CCA cell lines were highly inhibited by gemcitabine (IC50 = 13.35-16.0 M) whereas KKU-M214 was moderately inhibited by this drug (IC50 = 36.7 M). These least inhibited growths were found on KKU-100, KKU-M156 and KKU-M213 (IC50 = 406-4629 M).\  The generic (Gramagen) and the reference product (Gemza) formulations were not significantly different in their inhibitory effects on the all seven CCA cell lines.\ Conclusions: Although the inhibitory effect of gemcitabine was varied towards seven CCA cell lines, there was no difference in the IC50 values of the generic and reference formulations. Our findings indicate that the in vitro efficacy of these two formulations is similar.\ Keywords: growth inhibitory effect, gemcitabine, cholangiocarcinoma, generic formulation

Bioequivalence of Clozapine Tablet in Thai Schizophrenic Patients

Background: Clozapine is an atypical antipsychotic drug that has been used world wide for the treatment of schizophrenic patients. Several generic formulations of this drug are now available.\  In order to assure about the efficacy and safety of the generic formulation, it is necessary to compare the bioavailability between the generic and the reference formulations after administration to the patients.Purpose: To compare the bioavailabilty of two clozapine formulations, Clozapin (Pharmasant Laboratories Co., Ltd., Thailand) and Clozaril (Novartis Pharmaceuticals, UK) when administered to schizophrenic patients in the dose of 100 mg every 12 hr until the drug reach steady state.Study design : Multiple dose steady state, randomized crossover study under non-fasting condition.\  The study was approved by the Ethics Review Board of the Khon Kaen University and the Food and Drug Administration, Ministry of Public Health.Subject : 18 Male Thai schizophrenic patients Methods: The subjects received 100 mg of either the Clozapin or Clozaril\  per oral bid for 7 days. At day 7 of each study phase, the drug levels were reached the steady state/\  Two hour after meal, the drug was administered and\  blood samples were collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 hr. Plasma was separated and stored at \–80oC until assay. The plasma concentration of clozapine was determined by high performance liquid chromatography. Pharmacokinetic parameters were calculated from the plasma-concentration time profiles. The bioequivalence between the two formulations was assessed from the peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC0-12 ) ratios.\  Results: All subjects well tolerated both clozapine formulations. No serious adverse effects were reported. The Tmax, terminal half-life and the total plasma clearance of clozapine observed in the present study were comparable to those observed in other previous reports. All of the evaluated pharmacokinetic parameters between the Test and Reference formulations were of comparable. The 90% confident interval for the ratio of means for the LnCmax (0.9453-1.1182) and LnAUC0-12 (0.9734-1.0889) are within the guideline range of bioequivalence (0.80 to 1.25). Conclusion: The result demonstrated that the Test formulation, Clozapin was bioequivalent to the Reference formulation, Clozaril when orally administered in multiple \–dose to schizophrenic patients.

Bioequivalence Study of Ceftazidime by Intramuscular Administration in Healthy Thai Volunteers

Background : Ceftazidime is a third generation cephalosporin that has been commercially available through several manufacturers and distributors in Thailand because of its widely clinical use. However, there is no bioequivalent study of this drug in Thais.\  The present study was conducted to compare the in vivo bioequivalent of ceftazidime obtained from an original (reference), and a local (tested) manufacturer in healthy Thai volunteers.Objective: To determine if two ceftazidime preparations (Fortum and Forzid) of different manufacturers are bioequivalent when administered intramuscularly.Design: Double-blind single-dose, two-period, randomized crossover study.Subjects: Fourteen Healthy Thai Volunteers.Methods and Interventions: Ceftazidime 1 g was administered intramuscularly to subjects. Blood samples were collected at predetermined intervals and assayed for ceftazidime concentration with HPLC. Pharmacokinetic parameters were calculated from the observed plasma-concentration time profiles. Maximum plasma concentration (Cmax), time to peak concentration (Tmax), areas under the concentration-time curve from 0 to 12 h (AUC0-12) and 0 to infinity (AUC0-) were the primary parameters considered in the determination of bioequivalence.Results: The two ceftazidime preparations were generally well tolerated by all volunteers. Administration of both preparations resulted in similar mean values for every pharmacokinetic parameters. Statistical analysis revealed no significant difference between the two preparations in any parameter, indicating that the two preparations are statistically bioequivalent (p\<0.05). The 90% confident interval (CI) for the ratio of the means for the Cmax (0.9281-1.1272) and AUC0- (0.9311-1.0184), are within the Food and Drug Administration Guideline range of bioequivalence (0.80 to 1.25).Conclusions: These results demonstrated that the tested ceftazidime preparation (Forzid) is bioequivalent to the reference ceftazidime preparation (Fortum) when administered intramuscularly.

Herb and Drug Interaction

Abstract not available

Bioequivalence and Pharmacokinetic Study of Sildenafil in Healthy Thai Male Volunteers

Background: Sildenafil is a popular drug used for improving penile erectile function that has been commercially available through several manufacturers and distributors in Thailand. Therefore, it is necessary to study bioequivalence of the drugs obtained from the original manufacture and from a local manufacturer to ascertain that they can be medicated interchangeably.Objective: To determine whether two sildenafil preparations: Test (Erec®, Unison Laboratories, Co., Ltd., Thailand) and reference, (Viagra®, Pfizer Pty Limited., Australia) are bioequivalent.Design: Single oral dose and double-blind randomized two-way crossover.Population and samples: Fifteen healthy Thai male volunteers.Setting: Department of pharmacology, and Srinagarind Hospital, Faculty of Medicine, Khon Kaen University.Methods: The subjects received either 100 mg of the reference or test formulation. Blood samples were collected from catheter at several time points after sildenafil administration up to 12 hours. The bioequivalence between the two formulations was assessed by comparison of the peak plasma concentrations (Cmax) and area under the curve of time, from 0 to the last measurable concentration (AUC0-t last).Results: All subjects were well tolerated and presented no serious side effect. Statistical analysis revealed that the 90% confident intervals (CI) for the ratios between test and reference drugs of the log transformed the Cmax (0.8377-1.1985) and AUC0-t last (0.8610-1.1590), are within the Food and Drug Administration Guideline range of bioequivalence (0.80 to 1.25).Conclusions: It can be concluded that the 100 mg formulation of Test (Erec®) is bioequivalent to the Reference.Keywords: sildenafil, bioequivalence

Monoclonal Antibody: Targeted Therapy of Cancer

Abstract not available

Pharmacogenomics

Abstract not available