In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Caused by Cold Medicine Ingredients
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug hypersensitivities with high mortality. Typical over-the-counter drugs of cold medicines are suggested to be causative. As multiple ingredients are generally contained in cold medicines, it is of particular interest...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2013/514068 |
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| author | Hideto Isogai Hiroko Miyadera Mayumi Ueta Chie Sotozono Shigeru Kinoshita Katsushi Tokunaga Noriaki Hirayama |
| author_facet | Hideto Isogai Hiroko Miyadera Mayumi Ueta Chie Sotozono Shigeru Kinoshita Katsushi Tokunaga Noriaki Hirayama |
| author_sort | Hideto Isogai |
| collection | DOAJ |
| description | Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug hypersensitivities with high mortality. Typical over-the-counter drugs of cold medicines are suggested to be causative. As multiple ingredients are generally contained in cold medicines, it is of particular interest to investigate which ingredients are responsible for SJS/TEN. However, experimental examination of causal relationships between SJS/TEN and a particular drug molecule is not straightforward. Significant association between HLA-A*02:06 and SJS/TEN with severe ocular surface complications has been observed in the Japanese. In the present study, we have undertaken in silico docking simulations between various ingredients contained in cold medicines available in Japan and the HLA-A*02:06 molecule. We use the composite risk index (CRI) that is the absolute value of the binding affinity multiplied by the daily dose to assess the potential risk of the adverse reactions. The drugs which have been recognized as causative drugs of SJS/TEN in Japan have revealed relatively high CRI, and the association between SJS/TEN and HLA-A*02:06 has been qualitatively verified. The results have also shown that some drugs whose links to SJS/TEN have not been clinically recognized in Japan show the high CRI and suggested that attention should be paid to their adverse drug reactions. |
| format | Article |
| id | doaj-art-5305ffaed1cd4958b5b5ad61596d9b54 |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-5305ffaed1cd4958b5b5ad61596d9b542025-08-20T03:36:34ZengWileyJournal of Toxicology1687-81911687-82052013-01-01201310.1155/2013/514068514068In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Caused by Cold Medicine IngredientsHideto Isogai0Hiroko Miyadera1Mayumi Ueta2Chie Sotozono3Shigeru Kinoshita4Katsushi Tokunaga5Noriaki Hirayama6Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, 147 Shimokasuya, Isehara, Kanagawa 259-1143, JapanDepartment of Human Genetics, School of International Health, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Ophthalmology, Kyoto Prefectural University of Medicine, Hirokoji Kawaramachi, Kamigyo-ku, Kyoto 602-0841, JapanDepartment of Ophthalmology, Kyoto Prefectural University of Medicine, Hirokoji Kawaramachi, Kamigyo-ku, Kyoto 602-0841, JapanDepartment of Ophthalmology, Kyoto Prefectural University of Medicine, Hirokoji Kawaramachi, Kamigyo-ku, Kyoto 602-0841, JapanDepartment of Human Genetics, School of International Health, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanBasic Medical Science and Molecular Medicine, Tokai University School of Medicine, 147 Shimokasuya, Isehara, Kanagawa 259-1143, JapanStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug hypersensitivities with high mortality. Typical over-the-counter drugs of cold medicines are suggested to be causative. As multiple ingredients are generally contained in cold medicines, it is of particular interest to investigate which ingredients are responsible for SJS/TEN. However, experimental examination of causal relationships between SJS/TEN and a particular drug molecule is not straightforward. Significant association between HLA-A*02:06 and SJS/TEN with severe ocular surface complications has been observed in the Japanese. In the present study, we have undertaken in silico docking simulations between various ingredients contained in cold medicines available in Japan and the HLA-A*02:06 molecule. We use the composite risk index (CRI) that is the absolute value of the binding affinity multiplied by the daily dose to assess the potential risk of the adverse reactions. The drugs which have been recognized as causative drugs of SJS/TEN in Japan have revealed relatively high CRI, and the association between SJS/TEN and HLA-A*02:06 has been qualitatively verified. The results have also shown that some drugs whose links to SJS/TEN have not been clinically recognized in Japan show the high CRI and suggested that attention should be paid to their adverse drug reactions.http://dx.doi.org/10.1155/2013/514068 |
| spellingShingle | Hideto Isogai Hiroko Miyadera Mayumi Ueta Chie Sotozono Shigeru Kinoshita Katsushi Tokunaga Noriaki Hirayama In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Caused by Cold Medicine Ingredients Journal of Toxicology |
| title | In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Caused by Cold Medicine Ingredients |
| title_full | In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Caused by Cold Medicine Ingredients |
| title_fullStr | In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Caused by Cold Medicine Ingredients |
| title_full_unstemmed | In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Caused by Cold Medicine Ingredients |
| title_short | In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Caused by Cold Medicine Ingredients |
| title_sort | in silico risk assessment of hla a 02 06 associated stevens johnson syndrome and toxic epidermal necrolysis caused by cold medicine ingredients |
| url | http://dx.doi.org/10.1155/2013/514068 |
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