The effect of CYP3A5 genetic polymorphisms on adverse events in patients with ulcerative colitis treated with tacrolimus
Autor: | Mitsushige Sugimoto, Kenichiro Takahashi, Akira Andoh, Shigeki Bamba, Osamu Inatomi, Hirotsugu Imaeda, Ayumi Asada, Atsushi Nishida, Yukihiro Morita, Masaya Sasaki |
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Rok vydání: | 2017 |
Předmět: |
Male
medicine.medical_specialty Genotype Pharmacology Polymorphism Single Nucleotide 030226 pharmacology & pharmacy Gastroenterology Tacrolimus Nephrotoxicity 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine Remission Induction Therapy Cytochrome P-450 CYP3A Humans Medicine Adverse effect CYP3A5 Hepatology business.industry Acute Kidney Injury medicine.disease Ulcerative colitis Discontinuation Treatment Outcome Colitis Ulcerative Female 030211 gastroenterology & hepatology business Immunosuppressive Agents |
Zdroj: | Digestive and Liver Disease. 49:24-28 |
ISSN: | 1590-8658 |
Popis: | Background Tacrolimus is an immunosuppressive agent, used in the remission induction therapy of ulcerative colitis (UC). Aims We investigated the correlation between CYP3A5 genetic polymorphisms and the adverse events in patients with UC. The pharmacokinetics of tacrolimus after oral administration were also analyzed. Methods We enrolled 29 hospitalized patients with UC received oral tacrolimus. Genotyping for CYP3A5 A6986G (rs776746) was performed using Custom TaqMan® SNP genotyping assays. Adverse events, concentration and dose (C/D) ratios and clinical outcomes were investigated. Results CYP3A5 expressers and non-expressers were 16 and 13, respectively. C/D ratios of CYP3A5 expressers were significantly lower compared to non-expressers. The response rate in CYP3A5 non-expressers was relatively higher in the early phase of treatment compared to expressers, but not statistically significant. The incidence of overall adverse events was significantly higher in CYP3A5 expressers than in non-expressers (P = 0.034, chi-squared test). In particular, the incidence of nephrotoxicity was significantly higher in CYP3A5 expressers compared to non-expressers (P = 0.027, chi-squared test). All of the nephrotoxicity were reversible and resolved by discontinuation or dose reduction of tacrolimus. Conclusion The adverse events especially nephrotoxicity were frequently observed in CYP3A5 expressers. CYP3A5 expressers should be paid attention to the onset of nephrotoxicity. |
Databáze: | OpenAIRE |
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