Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Clin Chim Acta. 2011 Nov 20;412(23-24):2343-5. doi: 10.1016/j.cca.2011.06.040. Epub 2011 Jul 19.
Cytochrome P450 2C9 (CYP2C9) is the major isoform of the CYP2C subfamily, and is involved in the metabolism of many clinically important therapeutic agents. Here we describe a patient who was intolerant of warfarin treatment because of impaired drug metabolism related to the CYP2C9*3/*13 genotype and high warfarin sensitivity associated with the VKORC1 1173TT genotype.
A 64-year-old Korean man had taken warfarin for treatment of an occluded left subclavian artery and atrial fibrillation. Although the warfarin doses prescribed were not high (14 mg/week) during the induction of anticoagulation, the prothrombin time (PT) was elevated to over 120 s after two weeks of warfarin therapy. For this patient, a very low dose of warfarin (4 mg/week) was required in order to achieve target INR values.
To the best of our knowledge, this is the first report of a patient with CYP2C9*3/*13 and VKORC1 1173TT genotypes who had slower than normal warfarin metabolism, resulting in the need to administer an extremely low dose of warfarin in order to achieve the target INR value. Our report reinforces the relevance of pharmacogenetic testing to explain warfarin dose variability and to enable individualized dosage adjustments for improved warfarin treatment outcomes.
细胞色素 P450 2C9（CYP2C9）是 CYP2C 亚家族的主要同工酶，参与许多临床重要治疗药物的代谢。在这里，我们描述了一位因 CYP2C9*3/*13 基因型相关的药物代谢受损和 VKORC1 1173TT 基因型相关的华法林高敏感性而对华法林治疗不耐受的患者。
一位 64 岁的韩国男性因闭塞性左锁骨下动脉和心房颤动而接受华法林治疗。尽管在抗凝诱导期间华法林的剂量（每周 14 毫克）不高，但在两周的华法林治疗后，凝血酶原时间（PT）升高到超过 120 秒。对于该患者，需要极低剂量的华法林（每周 4 毫克）才能达到目标 INR 值。
据我们所知，这是首例 CYP2C9*3/*13 和 VKORC1 1173TT 基因型患者的报告，这些患者的华法林代谢速度比正常慢，导致需要给予极低剂量的华法林才能达到目标 INR 值。我们的报告强调了药物遗传学检测对于解释华法林剂量变异性以及实现个体化剂量调整以改善华法林治疗结果的相关性。
