Tett S E, Day R O, Cutler D J
Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Darlinghurst, Sydney, NSW, Australia.
J Rheumatol. 1993 Nov;20(11):1874-9.
To determine the relationship between hydroxychloroquine concentration and effect in patients with rheumatoid arthritis (RA).
Using a cross sectional study design, drug concentration and effect were measured at one time. Forty-three patients with RA, receiving hydroxychloroquine therapy for at least 6 months and not receiving glucocorticosteroids, gold or penicillamine therapy were enrolled. The main outcome measures were hydroxychloroquine concentration and disease activity measured as degree of synovitis, pain, duration and intensity of morning stiffness, impairment of activities of daily living, patients' and physicians' subjective assessment of disease, erythrocyte sedimentation rate, and rheumatoid factor (RF). Hemoglobin and albumin concentrations were also recorded.
Patients with none or mild intensity of morning stiffness, those with stiffness lasting less than 0.5 h and those with negative RF had significantly higher hydroxychloroquine blood concentrations than those in whom these measures indicated a more active disease (Mann-Whitney U test, p < 0.05). Similar trends were recorded for 3 other disease activity measures (p = 0.12-0.24). Analysis of all 9 individual disease activity measures indicated that the groups with less active disease had higher mean blood concentrations of hydroxychloroquine than those with measures indicating more active disease (p < 0.01).
Our data provide the first evidence of a concentration-response relationship for hydroxychloroquine in RA for individual disease activity measures. However, an unweighted summed score of disease activity did not correlate significantly with drug blood concentrations. A prospective study is necessary to confirm the relationship and to determine a therapeutic concentration range.
确定类风湿关节炎（RA）患者羟氯喹浓度与疗效之间的关系。
采用横断面研究设计，一次性测量药物浓度和疗效。纳入43例接受羟氯喹治疗至少6个月且未接受糖皮质激素、金制剂或青霉胺治疗的RA患者。主要观察指标为羟氯喹浓度和疾病活动度，疾病活动度通过滑膜炎程度、疼痛、晨僵持续时间和强度、日常生活活动能力受损情况、患者和医生对疾病的主观评估、红细胞沉降率及类风湿因子（RF）来衡量。同时记录血红蛋白和白蛋白浓度。
晨僵程度为无或轻度、晨僵持续时间少于0.5小时以及RF阴性的患者，其羟氯喹血药浓度显著高于那些上述指标提示疾病活动更明显的患者（Mann-Whitney U检验，p<0.05）。其他3项疾病活动指标也呈现类似趋势（p = 0.12 - 0.24）。对所有9项个体疾病活动指标的分析表明，疾病活动程度较低的组羟氯喹平均血药浓度高于疾病活动指标提示疾病活动更明显的组（p<0.01）。
我们的数据首次证明了在RA患者中，针对个体疾病活动指标，羟氯喹存在浓度-反应关系。然而，疾病活动度的未加权总分与药物血药浓度无显著相关性。有必要进行前瞻性研究以证实这种关系并确定治疗浓度范围。
