Genotypic and Phenotypic Characteristics of Co-Trimoxazole-Induced Cutaneous Adverse Reactions.

Background: Co-trimoxazole has been reported as a common culprit drug for various cutaneous adverse drug reactions (CADRs). However, information on genotypic and phenotypic characteristics is still limited. We aimed to study clinical characteristics, genetic suitability, laboratory findings, and treatment outcomes in patients with co-trimoxazole-induced CADR and determine variables associated with severe cutaneous adverse reactions (SCARs).

Implementation of Genotyping as Standard-of-Care for Reducing Carbamazepine/Oxcarbazepine Induced Cutaneous Adverse Drug Reactions in Thailand.

This study aimed to investigate the clinical impact of pharmacogenomics (PGx) testing before carbamazepine (CBZ)/oxcarbazepine (OXC) prescriptions and to determine whether this PGx testing was associated with the reduction of CBZ/OXC-induced cutaneous adverse drug reactions (CADRs) in Thailand. This retrospective observational cohort study was conducted by obtaining relevant PGx-testing and clinical data from electronic medical records during 2011-2020. 384 patient data were included in this study to investigate the clinical decision on CBZ/OXC usage before and after the PGx testing, and 1,539 patient data were included in this study to demonstrate the incidence of CBZ/OXC-induced SCARs and SJS between tested and non-tested patients.

Associations between UGT1A1 and SLCO1B1 polymorphisms and susceptibility to neonatal hyperbilirubinemia in Thai population.

Hyperbilirubinemia is the main mechanism that causes neonatal jaundice, and genetics is one of the risk factors of hyperbilirubinemia. Therefore, this study aims to explore the correlation between two genes, UGT1A1 and SLCO1B1, and hyperbilirubinemia in Thai neonates. One hundred thirty seven neonates were recruited from Division of Clinical Chemistry, Ramathibodi Hospital.

Evolution of Pharmacogenomics and the Importance of PGx Data Integration in Health Care System: A 10 Years Retrospective Study in Thailand.

The is the most polymorphic gene, play a crucial role in drug-induced hypersensitivity reactions. There is a lot of evidence associating several risk alleles to life-threatening adverse drug reactions, and a few of them have been approved as valid biomarkers for predicting life-threatening hypersensitivity reactions. The objective of this present study is to present the progression of pharmacogenomics (PGx) testing in the Thai population during a 10-year period, from 2011 to 2020.

as a Predictor of 6-Mercaptopurine-Induced Myelotoxicity in Thai Children with Acute Lymphoblastic Leukemia.

The response to 6-mercaptopurine (6-MP) can be altered by genetic polymorphisms in genes encoding drug-metabolizing enzymes and drug transporters. The purpose of this study was to investigate the association between genetic polymorphisms of drug-metabolizing enzymes ( > (), > and > ) and drug transporters ( > and > ) with 6-MP-related myelotoxicity and hepatotoxicity in Thai children with acute lymphoblastic leukemia (ALL). The prescribed dosage of 6-MP and its adverse effects were assessed from medical records during the first 8 weeks and 9-24 weeks of maintenance therapy.

Influence of Polymorphism on Plasma Efavirenz Concentration in Thai HIV-1 Patients.

Purpose: Plasma efavirenz (EFV) concentrations within therapeutic levels are essential to successfully treat patients suffering from human immunodeficiency virus (HIV) type 1. In addition to the drug-metabolizing enzyme CYP2B6, other phase II drug-metabolizing enzymes and transporters may have an important role in the pharmacokinetics of EFV. Thus, the influence of phase II drug-metabolizing enzymes and drug transporters on plasma EFV levels was investigated in Thai HIV patients receiving EFV.

Spectrum of cutaneous adverse reactions to aromatic antiepileptic drugs and human leukocyte antigen genotypes in Thai patients and meta-analysis.

Aromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens-Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population.

Genotyping alleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art.

Pharmacogenomics has great potential in reducing drug-induced severe cutaneous adverse drug reactions (SCARs). Pharmacogenomic studies have revealed an association between genes and SCARs including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Pharmacogenomics-guided therapy could prevent severe drug hypersensitivity reactions.

Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population.

Prior knowledge of allele frequencies of cytochrome P450 polymorphisms in a population is crucial for the revision and optimization of existing medication choices and doses. In the current study, the frequency of the CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2C19*6, CYP2C19*17, and CYP3A4 (rs4646437) alleles in a Thai population across different regions of Thailand was examined. Tests for polymorphisms of CYP2C9 and CYP3A4 were performed using TaqMan SNP genotyping assay and CYP2C19 was performed using two different methods; TaqMan SNP genotyping assay and Luminex x Tag V3.

Pharmacogenomics research and its clinical implementation in Thailand: Lessons learned from the resource-limited settings.

Several barriers present challenges to implementing pharmacogenomics into practice. This review will provide an overview of the current pharmacogenomics practices and research in Thailand, address the challenges and lessons learned from delivering clinical pharmacogenomic services in Thailand, emphasize the pharmacogenomics implementation issues that must be overcome, and identify current pharmacogenomic initiatives and plans to facilitate clinical implementation of pharmacogenomics in Thailand. Ever since the pharmacogenomics research began in 2004 in Thailand, a multitude of pharmacogenomics variants associated with drug responses have been identified in the Thai population, such as HLA-B∗15:02 for carbamazepine and oxcarbazepine, HLA-B∗58:01 for allopurinol, HLA-B∗13:01 for dapsone and cotrimoxazole, CYP2B6 variants for efavirenz, CYP2C9∗3 for phenytoin and warfarin, CYP3A5∗3 for tacrolimus, and UGT1A1∗6 and UGT1A1∗28 for irinotecan, etc.

Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients.

allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR).

Impact of CYP2C19, CYP3A4, ABCB1, and FMO3 genotypes on plasma voriconazole in Thai patients with invasive fungal infections.

Voriconazole is the first-line antifungal choice in the treatment of invasive fungal infections (IFIs). Single nucleotide polymorphisms (SNPs) in drug-metabolizing and transporter genes may affect voriconazole pharmacokinetics. This study aimed to determine the frequency of the CYP2C19 rs4244285, rs4986893, rs72552267, and rs12248560, CYP3A4 rs4646437, ABCB1 rs1045642, and FMO3 rs2266782 alleles and determine the association between these genetic variants and voriconazole concentrations in Thai patients with invasive fungal infections.

Genetic Diversity of Class I and Class II Alleles in Thai Populations: Contribution to Genotype-Guided Therapeutics.

Human leukocyte antigen (HLA) class I and II are known to have association with severe cutaneous adverse reactions (SCARs) when exposing to certain drug treatment. Due to genetic differences at population level, drug hypersensitivity reactions are varied, and thus common pharmacogenetics markers for one country might be different from another country, for instance, is associated with carbamazepine (CBZ)-induced SCARs in European and Japanese while is associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) among Taiwanese and Southeast Asian. Such differences pose a major challenge to prevent drug hypersensitivity when pharmacogenetics cannot be ubiquitously and efficiently translated into clinic.

Association between HLA-B Alleles and Carbamazepine-Induced Maculopapular Exanthema and Severe Cutaneous Reactions in Thai Patients.

The ∗ allele has been reported to have a strong association with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Thai patients. The alleles associated with carbamazepine-induced maculopapular exanthema (MPE) and the drug reaction with eosinophilia and systemic symptoms (DRESS) among the Thai population have never been reported. The aim of the present study was to carry out an analysis of the involvement of alleles in carbamazepine-induced cutaneous adverse drug reactions (cADRs) in the Thai population.

Association of and Alleles with Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Thai Population.

Lamotrigine (LTG) is commonly used for treatment of epilepsy and bipolar disorder. It is one of the common cause of cutaneous adverse drug reactions (CADR). Clinical symptoms of LTG-induced CADR range from maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCAR).

Dapsone-induced severe cutaneous adverse drug reactions are strongly linked with HLA-B*13: 01 allele in the Thai population.

Objectives: A previous publication in Chinese leprosy patients showed that the HLA-B*13:01 allele is a strong genetic marker for dapsone-induced drug hypersensitivity reactions, however there are no data describing whether HLA-B*13:01 is a valid marker for prediction of dapsone-induced drug hypersensitivity reactions in other ethnicities or nonleprosy patients. The aim of this study is to investigate whether there is an association between HLA genotypes and dapsone-induced severe cutaneous adverse reactions (SCARs) in Thai nonleprosy patients.

Patients And Methods: HLA-B genotypes of 15 patients with dapsone-induced SCARs (11 drug reaction with eosinophilia and systemic symptoms, 4 Stevens-Johnson syndrome/toxic epidermal necrolysis), 29 control patients, and 986 subjects from the general Thai population were determined by the reverse PCR sequence-specific oligonucleotides probe.

HLA-B (*) 58:01 for Allopurinol-Induced Cutaneous Adverse Drug Reactions: Implication for Clinical Interpretation in Thailand.

Background: The aim of this study was to investigate the predisposition to different types of allopurinol-induced cutaneous adverse drug reactions (CADR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN; SJS-TEN, n = 13), drug reaction with eosinophilia and systemic symptoms (DRESS, n = 10) and Maculopapular eruption (MPE; n = 7), conferred by HLA-B (*) 58:01 in a Thai population.

Methods: This case-control association study compares 30 patients with allopurinol-induced CADR, allopurinol-tolerant control patients (n = 100), and a Thai general population (n = 1095). Patients' human leukocyte antigen type B (HLA-B) alleles were genotyped by using a two-stage sequence-specific oligonucleotide probe system.

Development and Validation of Voriconazole Concentration by LC-MS-MS: Applied in Clinical Implementation.

Background: Voriconazole (VRZ) is a triazole antifungal used for treatment of invasive fungal infection, which is a life-threatening condition. Therapeutic drug monitoring is recommended for identifying the optimal dose in patients who have hepatic/renal impairment or reduced function of the CYP2C19 metabolizing enzyme.

Methods: One hundred microliters of sample plasma was extracted by protein precipitated with 200 μl of acetonitrile containing fluconazole as internal standard (IS).

A prospective observational study of CYP2C19 polymorphisms and voriconazole plasma level in adult Thai patients with invasive aspergillosis.

The aim of this study was to investigate the association of genetic variants of CYP2C19 (CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles) and voriconazole trough plasma concentrations in Thai patients with invasive fungal infection. A total of 285 samples from patients with invasive fungal infection and treated with voriconazole were prospectively enrolled. At steady state, trough voriconazole concentrations were measured using tandem mass spectrophotometry and high performance liquid chromatography.

HLA-B allele and haplotype diversity among Thai patients identified by PCR-SSOP: evidence for high risk of drug-induced hypersensitivity.

Background: There are 3 classes of HLA molecules; HLA class I, II and III, of which different classes have different functions. HLA-B gene which belongs to HLA class I play an important role predicting drug hypersensitivity.

Materials And Methods: Nine hundred and eighty-six Thai subjects who registered at a pharmacogenomics laboratory were determined for HLA-B genotype using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP).

Pharmacogenetics and clinical biomarkers for subtherapeutic plasma efavirenz concentration in HIV-1 infected Thai adults.

The aim of this study was to assess the influence of host genetic variations and clinical factors in relation to efavirenz level in HIV-1 infected Thai adults. A total of 100 HIV-infected subjects treated with efavirenz/lamivudine/tenofivir were prospectively enrolled. The panel of CYP2A6, CYP2B6 and CYP3A4/5 polymorphisms was genotyped.

CYP2C19 polymorphisms in the Thai population and the clinical response to clopidogrel in patients with atherothrombotic-risk factors.

Genetic variation in the cytochrome P450 2C19 (CYP2C19) gene has been documented gradually as the determinant conversion and variability in the antiplatelet effect of clopidogrel. The aims of this study were to determine the prevalence of clinically relevant allele variants (CYP2C19*2, CYP2C19*3, and CYP2C19*17) in a Thai study population, and finally determine whether the allele distributes and predicts metabolic phenotypes in clopidogrel treated patients. A total of 1,051 Thai patients participated in this study.

High plasma efavirenz concentration and CYP2B6 polymorphisms in Thai HIV-1 infections.

  Efavirenz is mainly metabolized by cytochrome P450 2B6 (CYP2B6). This study aimed to examine the frequencies of CYP2B6 and the association between CYP2B6 polymorphisms and plasma efavirenz concentrations in an HIV-1 infected Thai population. Mid-dose plasma efavirenz concentration was determined at 12 weeks following the initiation of an antiretroviral therapy (tenofovir, lamivudine and efavirenz) in 100 Thai adults with HIV-1 infection using high-performance liquid chromatography.