羟氯喹治疗自身免疫性疾病血药浓度影响因素分析

Blood concentration monitoring of hydroxychloroquine in patients with autoimmune diseases

目的:研究羟氯喹(hydroxychloroquine,HCQ)给药剂量、疗程、合并用药(激素、环磷酰胺、吗替麦考酚酯和甲氨蝶呤)及患者疾病类型、年龄、性别等因素对HCQ血药浓度的影响。方法:病例来自安徽医科大学第一附属医院风湿免疫科2017年7月至2018年6月长期(> 6个月)服用HCQ的自身免疫性疾病患者,谷浓度标本为当天患者服药前抽取静脉血获得。采用高效液相色谱法(high performance liquid chromatography,HPLC)监测患者全血中HCQ的血药浓度。采用SPSS 16. 0统计分析软件对相关数据进行统计学处理。结果:HCQ给药剂量为0. 4 g/d时血药浓度较高;年龄超过50岁的病人及HCQ治疗疗程超过10年的患者,HCQ血药浓度明显高于其他各组,结果存在统计学差异(P <0. 05),其他因素(疾病类型、患者性别及合并用药)对HCQ血药浓度无显著影响。且随着HCQ血药浓度增加,不良反应发生率增高。结论:HCQ的血药浓度主要受患者年龄、给药剂量及疗程的影响,0. 4 g/d给药,HCQ血药浓度较高;高龄及长期用药患者,适当降低HCQ剂量即可达到相同治疗效果;可通过监测HCQ血药浓度调整给药剂量,以减轻不良反应。

AIM:To explore the factors that influence the blood concentration of hydroxychloroquine(HCQ)including dosage,treatment course,and combination of the drug(hormone,cyclophosphamide,mycophenolate mofetil and methotrexate),as well as the disease type,age and gender of the patients.METHODS:During July 2017 to June 2018,blood samples were collected from autoimmune diseases patients who had been treated with HCQ for more than 6 months in department of rheumatology and immunology of our hospital.The blood concentration of HCQ was monitored by high performance liquid chromatography(HPLC).Statistical analyses were performed by SPSS 16.0.RESULTS:The blood concentration of HCQ was relatively high in patients treated with 0.4 g HCQ per day.Patients that over 50 years old and/or have been treated with HCQ for more than 10 years presented significant higher HCQ blood concentration(P<0.05).Other factors including disease type,gender and drug combination didn't obviously affect the concentration of HCQ.Moreover,we found that the incidence of adverse drug reactions was increased along with the increase of HCQ blood concentration.CONCLUSION:The blood concentration of HCQ is mainly affected by the dosage,the age of the patients,and the course of HCQ treatment.The equivalent therapeutic effect can be achieved with lower HCQ dosage in elderly and long-term treatment patients.Adjustment the dosage according to the blood HCQ concentration monitoring could decrease the incidence of adverse drug reactions.