在IBD患者的蒂奥瓜宁剂量的影响与TPMT缺乏症患者的TI
Debbie S Deben1, Luc J J Derijks2, Bianca J C van den Bosch3
1Department of Clinical Pharmacy, Clinical Pharmacology and Toxicology, Zuyderland Medical Centre, 6162 BG Sittard, The Netherlands.
Metabolites
|October 27, 2023
概括
提奥瓜宁是一种安全有效的治疗炎症性肠病 (IBD) 患者与异常的硫氨酸S-甲基转移酶 (TPMT) 代谢,当处方在降低剂量时. 密切监测确保了这些人的安全性和有效性.
科学领域:
- 药物基因组学 药物基因组学
- 胃肠病学 胃肠病学
- 临床药理学 临床药理学
背景情况:
- 氨酸S-甲基转移酶 (TPMT) 活性影响了氨酸药物的代谢和毒性.
- 异常的TPMT代谢是一种已知的药物不良事件的风险因素,在接受提奥普林的患者.
- 与阿扎西奥普林和默卡托普林相比,蒂奥瓜宁提供了一个不同的代谢途径,可能会改变其安全性.
研究的目的:
- 调查蒂奥瓜宁在炎症性肠病 (IBD) 中的安全性和有效性,这些患者的TPMT代谢中等或差.
- 确定最佳的剂量策略和预防措施,用于TIGUANINE在IBD患者的使用与TPMT的遗传变异.
- 描述临床结果,包括不良事件和治疗有效性,与tioguanine在这个患者群体相关.
主要方法:
- 追溯队列研究评估了485名在2016-2021年期间确定TPMT基因型的患者.
- 鉴定具有中级 (10.3%) 和低 (0.8%) TPMT代谢器状态的IBD患者.
- 对蒂奥瓜宁剂量,药物不良事件,实验室异常,治疗持续时间和异常TPMT基因型患者的有效性进行分析.
主要成果:
- 降低的蒂奥瓜宁剂量 (中级患者每天5毫克,TPMT代谢较差患者每两周10毫克) 与安全有效的长期治疗有关.
- 一个较差的TPMT代谢器在标准剂量为10毫克/天时经历了延迟的泛细胞衰竭.
- 降低TPMT活性与药物动力学转变相关,可能导致标准瓜氨酸剂量的晚发性骨髓毒性.
结论:
- 当使用大大降低剂量方案时,蒂奥瓜宁可以成为IBD患者具有功能障碍的TPMT的安全和有效的治疗选择.
- 严格的治疗药物监测和安全监测对于在TPMT变异患者中管理蒂奥瓜宁至关重要.
- 基于TPMT基因型的个性化剂量策略对于优化IBD中蒂冈治疗至关重要.
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