人类水解酶的调节及其对药理动力学和药理动力学的影响
1Departments of Pharmaceutical Sciences (S.M.J.) and Clinical Pharmacy (H.-J.Z.), University of Michigan, Ann Arbor, Michigan.
概括
遗传和非遗传因素显著影响酶酶,影响药物代谢. 了解这些调节剂可以通过个性化治疗方案来提高药物的疗效和安全性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 酶学 是一种酶学.
- 药物新陈代谢 药物新陈代谢
背景情况:
- 水解酶是代谢许多必需药物的关键酶.
- 酶活性的个体差异导致药物药理动力学 (PK) 和药理动力学 (PD) 的显著变化.
- 酶表达和活性的调节受遗传和非遗传因素的影响.
研究的目的:
- 审查目前对六种关键酸酶的遗传和非遗传调节者的理解.
- 探索遗传变异和非遗传因素对酶活性和药物PK/PD的影响.
- 为了强调与其他药物代谢酶相比,水解酶的研究不足.
主要方法:
- 文献综述侧重于遗传多态性和非遗传调节剂 (抑制剂,诱导剂).
- 对发育表达模式和性别差异的分析,如有.
- 检查对基质药物的 PK 和 PD 的作用,这些药物用于碳素化酶 (CES) - 1 ,CES2 ,亚拉胺脱乙酸酶 (AADAC),偏氧酶 (PON) - 1 ,PON3 和甲素A (CTSA).
主要成果:
- 确定了许多影响酶表达,活性和相关药物PK/PD的遗传和非遗传调节剂.
- 由于遗传和非遗传因素,酶活性存在显著的变异性.
- 水溶酶通常没有得到充分的研究,对于大多数监管者来说,其确定的临床意义有限.
结论:
- 了解酶调节机制是完善治疗策略的关键.
- 个性化医疗方法可以通过了解个体的酶活性来增强.
- 需要进一步的研究来确定酶调节剂对改善药物疗效和安全的临床意义.
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