Pharmacogenetic Markers of Drug Hypersensitivity in a Thai Population.

Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS) are potentially life-threatening cutaneous reactions caused by several drugs. Recently, a number of genes encoding for human antigen presenting proteins, alleles, have been discovered as valid pharmacogenetic markers for prediction of these life-threatening reactions. This study was aimed to determine the distribution of alleles including the class I and class II genes in 183 unrelated individuals of a Thai population using high resolution genotyping in order to obtain 2-field data (4-digit resolution) and compare the frequencies of the alleles that have been proposed as markers of SCARs with other ethnics.

Comparison between the Allele and Single-Nucleotide Polymorphisms in Chromosome 6 for Prediction of Allopurinol-Induced Severe Cutaneous Adverse Reactions.

Severe cutaneous adverse drug reactions (SCARs) are life-threatening reactions. The strong association between the allele and allopurinol-induced SCARs is well recognized. Screening for allele before prescribing allopurinol in some populations has been recommended.

Risk factors of allopurinol-induced severe cutaneous adverse reactions in a Thai population.

Background: Allopurinol is one of the most common causes of severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This study identified the risk factors associated with the development of allopurinol-induced SCARs in a Thai population.

Patients And Methods: Eighty-six allopurinol-induced SCARs (i.

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.

In vitro-in vivo extrapolation of CYP2C8-catalyzed paclitaxel 6α-hydroxylation: effects of albumin on in vitro kinetic parameters and assessment of interindividual variability in predicted clearance.

Objectives: This study aimed to characterize the effects of bovine serum albumin (BSA) on the kinetics of CYP2C8-catalyzed paclitaxel 6α-hydroxylation in vitro; determine whether the addition of BSA to incubations improves the prediction of paclitaxel hepatic clearance via this pathway in vivo; and assess interindividual variability in predicted clearance.

Methods: The kinetics of paclitaxel 6α-hydroxlation by human liver microsomes (HLM) and recombinant CYP2C8 were characterized in incubations performed with and without BSA (2% w/v) supplementation, and the in vitro kinetic data were extrapolated to provide estimates of in vivo clearances. The Simcyp population-based ADME simulator was used to determine interindividual variability in the predicted clearances.

Inhibitory effects of Phyllanthus amarus and its major lignans on human microsomal cytochrome P450 activities: evidence for CYP3A4 mechanism-based inhibition.

Phyllanthus amarus has long been used as a herbal medicine in several countries. Phytochemicals in herbal medicine may interact with cytochromes P450 (CYP) and thus raise the potential of herb-drug interactions; therefore, the inhibitory effects of P. amarus and its major phytochemicals phyllanthin and hypophyllanthin on CYP isoforms were determined using human liver microsomes and selective substrates.

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.

Albendazole therapy for eosinophilic meningitis caused by Angiostrongylus cantonensis.

Eosinophilic meningitis in humans is commonly caused by the nematode Angiostrongylus cantonensis. A severe headache is the most common presenting symptom. A prospective, randomized, double-blind, placebo, controlled study was conducted to determine if albendazole was efficacious in relieving such headaches.

CYP2C19 genetic polymorphism in Thai, Burmese and Karen populations.

The genetic polymorphism of CYP2C19 was examined in three Southeast Asian populations. This study was conducted in 774 Thais, 127 Burmeses and 131 Karens. Genomic DNA was extracted from leucocytes and analyzed by the PCR-RFLP technique.

Steady-state bioequivalence study of clozapine tablet in schizophrenic patients.

Purpose: To compare the bioavailability of two clozapine formulations (100 mg Clozaril tablet from Novartis Pharmaceuticals UK Ltd., UK, as a Reference formulation and 100 mg Cloril tablet from Atlantic Laboratories Corp., Ltd.

Contamination of aflatoxins in herbal medicinal products in Thailand.

Twenty-eight herbal medicinal products from Thailand were investigated for aflatoxin (AF) contaminations by employing a specific HPLC assay for the determination of AFB1, B2, G1 and G2. The samples were extracted with 80% (v/v) methanol in water before further cleaned up with an immunoaffinity column and followed by the detection of AFs by using an electrochemically post-column derivatization with iodine and fluorescence detector. The extraction procedure was optimized in order to obtain the best recovery.

Thiopurine S-methyltransferase genetic polymorphism in the Thai population.

Aims: To determine the incidence of the thiopurine S-methyltransferase (TPMT) genetic polymorphism in the Thai population.

Methods: Genomic DNAs were isolated from peripheral blood leucocytes of 200 healthy Thais. The frequencies of five allelic variants of the TPMT gene, TPMT*2, *3A, *3B, *3C and *6 were determined using allele specific polymerase chain reaction (PCR) or PCR-Restriction fragment length polymorphism technique.

Analysis of the CYP2C19 polymorphism in a North-eastern Thai population.

CYP2C19 is a polymorphically expressed cytochrome P450 responsible for the metabolism of several clinically used drugs, including some barbiturates, diazepam, proguanil, propranolol and several proton pump inhibitors. Genetic polymorphism of this enzyme shows marked interracial differences, with the poor metabolizer (PM) phenotype representing 2-5% of Caucasian and 11-23% of Oriental populations. In the present study, CYP2C19 phenotype and genotype were investigated in 107 North-eastern Thai subjects using the omeprazole hydroxylation index (HI) and polymerase chain reaction-restriction fragment length polymorphism technique, respectively.