Berta E, Harangi M, Zsíros N, Nagy E V, Paragh G, Bodor M
Pharmazie. 2014 Jun;69(6):420-3.
Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP3A4, 2C9 and 2C19 are common in our patients with statin induced adverse effects. Normalizing the thyroid hormone status and optimizing of the concomitant medication may reduce the risk of statin induced adverse effects.
他汀类药物是预防心血管疾病的有效治疗药物，在全球范围内广泛使用。然而，他汀类药物引起的不良反应是最大限度降低心血管风险的主要障碍。甲状腺功能减退以及服用在他汀类药物生物转化所发生的相同细胞色素P450（CYPP450）途径上代谢的药物，是他汀类药物引起包括肌病在内的不良反应的重要危险因素。辛伐他汀、阿托伐他汀和洛伐他汀由CYP3A4代谢，氟伐他汀由CYP2C9代谢，而瑞舒伐他汀由CYP2C9和2C19代谢。我们调查了101例患有他汀类药物引起的不良反应（包括肌病56例；55.4%）、肝病（39例；38.6%）和胃肠道不良反应（24例；23.8%）的高脂血症患者（年龄61.3±9.9岁）的游离甲状腺激素水平和伴随用药的CYP代谢情况。5例患者（4.95%）甲状腺激素水平异常；2例临床甲状腺功能减退，3例甲状腺功能亢进。11例患者有甲状腺功能减退病史（10.9%）。1例甲状腺功能减退患者和2例甲状腺功能亢进患者发生了肌病。他汀类药物引起的肌病患者与其他类型不良反应患者的促甲状腺激素（TSH）、游离甲状腺素（fT4）和游离三碘甲状腺原氨酸（fT3）水平无显著差异。78例患者（77.2%）服用了也被他汀类药物使用的CYP同工酶代谢的药物（CYP3A4：66例（65.3%）；CYP2C9：67例（66.3%）；CYP2C19：54例（53.5%））。与其他类型不良反应患者相比，肌病患者服用CYP3A4代谢的药物明显更多（p<0.05）。辛伐他汀治疗的患者中肌病病例更多（52%对38%，无统计学差异），而与其他类型他汀类药物引起的不良反应患者相比，氟伐他汀治疗的患者中肌病患者明显更少（13%对33%，p<0.05）。在我们患有他汀类药物引起不良反应的患者中，甲状腺激素状态异常以及服用CYP3A4、CYP2C9和CYP2C19代谢的药物都很常见。使甲状腺激素状态正常化并优化伴随用药可能会降低他汀类药物引起不良反应的风险。
