NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine.

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP.

Genetic Polymorphisms of Drug-Metabolizing Enzymes Involved in 6-Mercaptopurine-Induced Myelosuppression in Thai Pediatric Acute Lymphoblastic Leukemia Patients.

Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 ( ) genes have been proposed as key determinants of 6-mercaptopurine (6-MP)-induced myelosuppression in pediatric acute lymphoblastic leukemia (ALL). In the present study, genotypes of and were investigated in 178 Thai pediatric patients with ALL by the TaqMan SNP genotyping assay and DNA sequencing. The frequency of was 0.

Therapeutic concentration achievement and allograft survival comparing usage of conventional tacrolimus doses and CYP3A5 genotype-guided doses in renal transplantation patients.

Aims: Although cytochromeP450(CYP)3A5 gene polymorphism affects personalized tacrolimus doses, there is no consensus as to whether CYP3A5 genotypes should be determined to adjust the doses. The aims were to compare the therapeutic ranges and clinical outcomes between the conventional and genotype-guided tacrolimus doses.

Methods: This randomized controlled study compared 63 cases of the conventional tacrolimus dose group (0.

Effect of CYP3A5 genotype on hospitalization cost for kidney transplantation.

Background Dosage quantities of tacrolimus (TAC) vary according to cytochrome P450 3A5 (CYP3A5) genotype. Genotyping is expected to optimize the response to TAC response and to minimize adverse effects. In Thailand, kidney transplantation is reimbursable with the same diagnosis-related group payment regardless of patient's CYP3A5 genotype.

Genetic Polymorphisms Associated With Increased Defibrillator Shocks in Brugada Syndrome.

Background: Brugada syndrome (BrS) is an inherited primary arrhythmia disorder leading to sudden cardiac arrest. , encoding the α-subunit of the cardiac sodium channel (Nav1.5), is the most common pathogenic gene of BrS.

The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients.

Purpose: The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients.

Methods: A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.

Outcomes of a Randomized Controlled Trial Comparing Modified High Dose Omeprazole and Amoxicillin Triple Therapy with Standard Triple Therapy for Helicobacter Pylori Eradication.

Background: Helicobacter pylori (H. pylori) infection is related to peptic ulcer diseases and gastric cancer and eradication of H. pylori should be expected to decrease the risk of their development.

Comparative pharmacodynamic effects of two clopidogrel formulations under steady-state conditions in healthy Thai volunteers .

Objective: Clopidogrel is a commonly used antiplatelet aggregation agent. Compared with the reference clopidogrel product, most commercially available generic clopidogrel products contain different crystalline forms of clopidogrel. This study was aimed to compare the pharmacodynamics of a commonly used generic clopidogrel product in Thailand with the reference clopidogrel product under steady state conditions.

Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population.

Background: Phenytoin is one of the most common causative drugs of several types of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS). Genetic polymorphisms of the human leukocyte antigens (HLA) and cytochromes P450 (CYP) have been proposed as key elements for the susceptibility to phenytoin-related SCAR in certain ethnicities. This study investigated the associations between the genetic polymorphisms of HLA class I and CYP2C9 and phenytoin-related SCAR in a Thai population.

The impact of genetic polymorphisms of drug metabolizing enzymes on the pharmacodynamics of clopidogrel under steady state conditions.

Clopidogrel is an antiplatelet drug that requires biotransformation steps to its active metabolite via cytochromes P450 (CYP), particularly CYP2C19 and CYP3A5 as well as paraoxonase-1 (PON1). The impact of CYP3A5 and PON1 genetic polymorphisms on the response of this drug is unclear. This study aimed to elucidate the degree of genetic polymorphisms of key drug metabolizing enzymes on the antiplatelet effect of clopidogrel.

Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions.

Background: Co-trimoxazole is a sulfonamide-containing antibiotic that is effective in the treatment of several infections and for prophylaxis of Pneumocystis jiroveci pneumonia. This drug has been reported as a common culprit drug for the Stevens-Johnson syndrome (SJS) and for toxic epidermal necrolysis (TEN). Human leukocyte antigens (HLAs) play a key role in the immunopathogenesis of severe cutaneous reactions induced by several drugs.

Non-BMPR2 mutation heritable pulmonary arterial hypertension in Southeast Asia.

A 29-year-old Thai man presented with progressive dyspnea and evidence of pulmonary hypertension. Computed tomography was negative for pulmonary embolism. Cardiac catheterization confirmed the diagnosis of pulmonary arterial hypertension (mean pulmonary artery pressure 54 mm Hg, left ventricular end-diastolic pressure 4 mm Hg, and pulmonary vascular resistance 25 Wood units) without an intracardiac shunt.

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

Introduction: 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.

Personalized tacrolimus doses determined by CYP3A5 genotype for induction and maintenance phases of kidney transplantation.

Background: Cytochrome P450 (CYP) 3A4 and 3A5 are major isoforms involved in the metabolism of tacrolimus, with the CYP3A5 gene being more polymorphic. It is hypothesized that individual variation in the metabolism of tacrolimus drug may result from genetic polymorphism of CYP3A5. It has been reported that the clearance of tacrolimus in patients with the CYP3A5*1 allele was ~2.

Comparative bioavailability of two moxifloxacin tablet products after single dose administration under fasting conditions in a balanced, randomized and cross-over study in healthy volunteers.

Moxifloxacin, a 4th generation of fluoroquinolones, is a broad spectrum antibacterial agent against respiratory tract pathogens, including Gram-positive and Gram-negative bacteria, anaerobic bacteria and atypical respiratory tract pathogens. In order to evaluate the efficacy and safety of generic moxifloxacin products, the bioequivalence of these generic products with an approved reference formulation should be demonstrated. Thus, the aim of this study was to compare the rate and extent of absorption of a new generic film coated moxifloxacin tablet product (Rapiflox®, Atlantic Laboratories Corporation Ltd.

HLA-B*1502 strongly predicts carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Thai patients with neuropathic pain.

Background: Carbamazepine (CBZ) is one of the standard pharmacological treatments for neuropathic pain. However, its serious adverse drug reactions include Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Recently, HLA-B*1502 allele was implicated as a genetic marker of CBZ-induced SJS/TEN in some Asian epilepsy populations.

Thiopurine S-methyltransferase pharmacogenetics: functional characterization of a novel rapidly degraded variant allozyme.

A novel human thiopurine S-methyltransferase (TPMT) variant allele, (319 T>G, 107Tyr>Asp, *27), was identified in a Thai renal transplantation recipient with reduced erythrocyte TPMT activity. The TPMT*27 variant allozyme showed a striking decrease in both immunoreactive protein level and enzyme activity after transient expression in a mammalian cell line. We set out to explore the mechanism(s) responsible for decreased expression of this novel variant of an important drug-metabolizing enzyme.

The influence of CYP2A6 polymorphisms and cadmium on nicotine metabolism in Thai population.

We investigated the influence of genetic, cadmium exposure and smoking status, on cytochrome P450-mediated nicotine metabolism (CYP2A6) in 182 Thai subjects after receiving 2mg of nicotine gum chewing for 30min. The urinary excretion of cotinine was normally distributed over a 2h period (logarithmically transformed). Individuals with urinary cotinine levels in the ranges of 0.

Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population.

Objectives: Allopurinol, a uric acid lowering drug commonly used for hyperuricemia and gouty arthritis, has been reported as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between allopurinol-induced SCAR and HLA-B*5801 was observed in a Han Chinese population with high frequency of this allele, whereas only a moderate association was observed in populations with low frequency (i.e.

Impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand.

Background: Thiopurine S-methyltransferase (TPMT) is a polymorphic enzyme associated with detoxification of azathioprine, an immunosuppressant used after renal transplantation in several Asian countries. Patients with variations of the TPMT gene may be at risk for myelosuppression after they receive a standard dosage of the drug. The frequency of TPMT*3C has been reported to be higher in the Thai population than in other Asian populations, possibly putting the Thais at higher risk for myelosuppression.

Acute valproic acid overdose: enhance elimination with multiple-doses activated charcoal.

Multiple dose activated charcoal (MDAC) is used to enhance elimination of toxic substance in acute poisoning. However, its role in acute valproic acid (VA) overdose is controversial. The authors report a case of VA overdose that successfully recovered with MDAC treatment.

Predictive risk factors of seizure-related injury in persons with epilepsy.

Objective: The clinical risk factors for seizure-related injuries (SRI) in adult persons with epilepsy (PWE) were studied and analyzed to develop a predictive model.

Methods: We enrolled 300 consecutive cases from three epilepsy clinics in Northeast, Thailand. Subjects were eligible if reported to have at least one seizure attack during the past 12 months.

Very high dose phenobarbital for refractory status epilepticus.

Background: Refractory status epilepticus (RSE), defined as status epilepticus that fails to respond to first, second and third-line therapy. The RSE is associated with high morbidity and mortality. Treatment guidelines of RSE give a spectrum of options, such as, continuous intravenous (i.

Basic knowledge of epilepsy among medical students.

Background: The medical students' knowledge about basic medical neuroscience in the preclinical level may be fragmented and incomplete.

Objective: Evaluate the knowledge of students prior to a lecture on epilepsy in clinical level.

Material And Method: One hundred ten fourth-year medical students' knowledge was accessed by a self-administered questionnaire.

Ceftazidime overdose-related nonconvulsive status epilepticus after intraperitoneal instillation.

We report a case of ceftazidime-related nonconvulsive status epilepticus (NCSE) in a 70-year-old female patient with continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. She was given ceftazidime intravenously which was then changed to intraperitoneal installation after clinical improvement. She received 11 g of ceftazidime via intraperitoneal installation for two days after being discharged from the hospital.