期刊
DRUG METABOLISM AND PHARMACOKINETICS
卷 47, 期 -, 页码 -出版社
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.1016/j.dmpk.2022.100480
关键词
Co-trimoxazole; Severe cutaneous adverse reactions; SCARs; SJS; TEN; DRESS; HLA; Drug -metabolizing enzymes
资金
- Health System Research Institute under Genomics Thailand Strategic Fund (HSRI) [65-038]
- Young Researcher Development Project of Khon Kaen University
This study found that the HLA-B*13:01 allele is significantly associated with Co-trimoxazole-induced SCARs, especially DRESS, while the HLA-C*08:01 allele is significantly associated with Co-trimoxazole-induced SJS/TEN in HIV/AIDS patients. The genes involved in the bioactivation and detoxification of Co-trimoxazole investigated in this study do not play a major role in the development of all phenotypes of SCARs.
Co-trimoxazole is mainly used as a first-line drug for treatment and prophylaxis against Pneumocystis jiroveci pneumonia. This drug, however, has been reported as the most common causative drug for severe cutaneous adverse reactions (SCARs). This study aimed to extensively elucidate the associations between genetic polymorphisms of HLA class I and genes involved in bioactivation and detoxification of co-trimoxazole on co-trimoxazole-induced SCARS in a large sample size and well-defined Thai SCARs pa-tients. A total of 67 patients with co-trimoxazole-induced SCARs, consisting of 51 SJS/TEN patients and 16 DRESS patients, and 91 co-trimoxazole tolerant controls were enrolled in the study. The results clearly demonstrated that the HLA-B*13:01 allele was significantly associated with co-trimoxazole-induced SCARs, especially with DRESS (OR = 8.44, 95% CI = 2.66-26.77, P = 2.94 x 10-4, Pc = 0.0126). More-over, the HLA-C*08:01 allele was significantly associated with co-trimoxazole-induced SJS/TEN in the HIV/ AIDS patients with an OR of 8.51 (95% CI = 2.18-33.14, P = 8.60 x 10-4, Pc = 0.0241). None of the genes involved in the bioactivation and detoxification of co-trimoxazole investigated in this study play any major role in the development of all phenotypes of SCARs.(c) 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
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