Yeon Lee Ji, Lee Jennifer, Ki Kwok Seung, Hyeon Ju Ji, Su Park Kyung, Park Sung-Hwan
Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea.
Arthritis Care Res (Hoboken). 2017 Apr;69(4):536-542. doi: 10.1002/acr.22962. Epub 2017 Mar 7.
To identify factors associated with blood concentrations of hydroxychloroquine (HCQ) and its major metabolite, N-desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE; lupus) receiving long-term oral HCQ treatment.
SLE patients who had been taking HCQ for more than 3 months were recruited. Various clinical characteristics, laboratory values, and SLE Disease Activity Index (SLEDAI) scores were examined. The concentrations of HCQ and DHCQ ([HCQ] and [DHCQ]) were measured by liquid chromatography mass spectrometry, and the relationship between [HCQ], [DHCQ], and [HCQ]:[DHCQ] ratio to various factors was investigated.
In total, 189 SLE patients receiving long-term HCQ treatment were included in the analysis. The median (interquartile range [IQR]) [HCQ] was 515 (IQR 353-720) ng/ml, the median [DHCQ] was 417 (IQR 266-591) ng/ml, and the median [HCQ]:[DHCQ] ratio was 1.3 (range 1.0-1.7). [HCQ] was closely associated with [DHCQ] (r = 0.81, P < 0.0001). The weight-adjusted oral HCQ dose was strongly associated with both [HCQ] (P < 0.001) and [DHCQ] (P < 0.001). Time since last dose was associated with [HCQ] (P < 0.001). No statistically significant association was found between renal function or smoking and [HCQ] or [DHCQ]. Use of additional immunosuppressants increased both [HCQ] and [DHCQ] after adjusting for possible confounders (P = 0.04 and P = 0.03, respectively). The lower SLEDAI score was significantly related to higher [HCQ], after adjusting for age, sex, weight-adjusted HCQ dose, time since last dose, number of other immunosuppressants, and smoking status (P = 0.007).
Various factors affected blood levels of [HCQ], [DHCQ], or the [HCQ]:[DHCQ] ratio of SLE patients receiving long-term oral HCQ treatment. Notably, higher [HCQ] was associated with a lower SLEDAI score in our typical outpatient clinic population with lupus.
确定接受长期口服羟氯喹（HCQ）治疗的系统性红斑狼疮（SLE；狼疮）患者中，与羟氯喹及其主要代谢产物N - 去乙基羟氯喹（DHCQ）血药浓度相关的因素。
招募服用HCQ超过3个月的SLE患者。检查各种临床特征、实验室值和SLE疾病活动指数（SLEDAI）评分。通过液相色谱质谱法测量HCQ和DHCQ的浓度（[HCQ]和[DHCQ]），并研究[HCQ]、[DHCQ]以及[HCQ]：[DHCQ]比值与各种因素之间的关系。
总共189名接受长期HCQ治疗的SLE患者纳入分析。[HCQ]的中位数（四分位间距[IQR]）为515（IQR 353 - 720）ng/ml，[DHCQ]的中位数为417（IQR 266 - 591）ng/ml，[HCQ]：[DHCQ]比值的中位数为1.3（范围1.0 - 1.7）。[HCQ]与[DHCQ]密切相关（r = 0.81，P < 0.0001）。体重调整后的口服HCQ剂量与[HCQ]（P < 0.001）和[DHCQ]（P < 0.001）均密切相关。距上次服药时间与[HCQ]相关（P < 0.001）。未发现肾功能或吸烟与[HCQ]或[DHCQ]之间存在统计学上的显著关联。在调整可能的混杂因素后，使用额外的免疫抑制剂会使[HCQ]和[DHCQ]均升高（分别为P = 0.04和P = 0.03）。在调整年龄、性别、体重调整后的HCQ剂量、距上次服药时间、其他免疫抑制剂数量和吸烟状况后，较低的SLEDAI评分与较高的[HCQ]显著相关（P = 0.007）。
多种因素影响接受长期口服HCQ治疗的SLE患者的[HCQ]、[DHCQ]血药水平或[HCQ]：[DHCQ]比值。值得注意的是，在我们典型的狼疮门诊患者群体中，较高的[HCQ]与较低的SLEDAI评分相关。
