Tacrolimus-modified release formulations allow for once-daily dosing, and adherence is better compared to the twice-daily immediate release formulation. When patients are switched from one formulation to another, variable changes in drug concentrations are observed. Current data suggest that the changes in drug exposure are larger in patients who express the CYP3A5 enzyme (CYP3A5 *1/*3 or *1/*1) compared to nonexpressers (CYP3A5*3/*3). Possibly, these differences are due to the fact that in the upper region of the small intestine CYP3A activity is higher, and that this expression of CYP3A decreases towards the more distal parts of the gut. Modified release formulations may therefore be subject to a less presystemic metabolism. However, the full implications of pharmacogenetic variants affecting the expression and function of drug transporters in the gut wall and of enzymes involved in phase I and phase II metabolism on the different formulations are incompletely understood, and additional studies are required. Conclusions: In all patients in whom the formulation of tacrolimus is changed, drug levels need to be checked to avoid clinically relevant under- or overexposure. In patients with the CYP3A5 expresser genotype, this recommendation is even more important, as changes in drug exposure can be expected.

中文翻译：

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药物遗传变异对缓释和速释他克莫司制剂 PK 影响的比较

他克莫司调释制剂允许每天给药一次，与每天两次的立即释放制剂相比，依从性更好。当患者从一种制剂切换到另一种制剂时，观察到药物浓度的可变变化。目前的数据表明，与非表达者（CYP3A5*3/*3）相比，表达 CYP3A5 酶（CYP3A5 *1/*3 或 *1/*1）的患者的药物暴露变化更大。可能，这些差异是由于在小肠上部区域 CYP3A 活性较高，并且 CYP3A 的这种表达向肠道更远端部分降低。因此，缓释制剂可能经受较少的系统前代谢。然而，药物遗传变异影响肠壁药物转运蛋白的表达和功能以及参与 I 期和 II 期代谢的酶对不同制剂的全部影响尚不完全清楚，需要进一步研究。结论：在改变他克莫司配方的所有患者中，需要检查药物水平以避免临床相关的暴露不足或过度暴露。对于具有 CYP3A5 表达基因型的患者，此建议更为重要，因为可以预期药物暴露会发生变化。需要检查药物水平以避免临床相关的暴露不足或过度暴露。对于具有 CYP3A5 表达基因型的患者，此建议更为重要，因为可以预期药物暴露会发生变化。需要检查药物水平以避免临床相关的暴露不足或过度暴露。对于具有 CYP3A5 表达基因型的患者，此建议更为重要，因为可以预期药物暴露会发生变化。