Duricová J, Grundmann M
Ostravská univerzita, Zdravotne-sociální fakulta, Ustav klinické farmakologie FN, Ostrava.
Ceska Slov Farm. 2007 Oct;56(5):220-4.
The calcineurin inhibitors cyclosporine (CsA) and tacrolimus (Tac) are widely used in the prevention of acute rejection after solid organ transplantation. However, their clinical use is associated with many adverse reactions. The calcineurin inhibitors CsA and Tac have a narrow therapeutic index and show highly variable pharmacokinetics. The low CsA and Tac bioavailability has been attributed to interindividual differences in the expression of the metabolizing enzyme cytochrome P450 3A. The genes for CYP3A4 and 3A5 undergo genetic polymorphism. The results of many studies focusing on the impact of CYP 3A polymorphism on CsA and Tac pharmacokinetics are clear with Tac, where an association between CYP 3A polymorphism and the pharmacokinetic consequences has been shown. However, the results with CsA are controversial.
钙调神经磷酸酶抑制剂环孢素(CsA)和他克莫司(Tac)被广泛用于预防实体器官移植后的急性排斥反应。然而,它们的临床应用伴随着许多不良反应。钙调神经磷酸酶抑制剂CsA和Tac的治疗指数较窄,且药代动力学表现出高度的变异性。CsA和Tac的低生物利用度归因于代谢酶细胞色素P450 3A表达的个体差异。CYP3A4和3A5基因存在基因多态性。许多关注CYP 3A多态性对CsA和Tac药代动力学影响的研究结果,对于Tac来说是明确的,已表明CYP 3A多态性与药代动力学结果之间存在关联。然而,CsA的研究结果存在争议。