Department of Pharmaceutics and Pharmacometrics, School of Pharmacy, Shujitsu University, Okayama, Japan.
Department of Drug Metabolism and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Aomori University, Aomori, Japan.
Mod Rheumatol. 2023 Aug 25;33(5):953-960. doi: 10.1093/mr/roac113.
Reduction of the hydroxychloroquine (HCQ) dosage is recommended in systemic lupus erythematosus (SLE) patients with renal impairment, but a pharmacokinetics (PK) study of patients with renal impairment has not yet been performed.
We investigated the PK of both single and multiple doses of HCQ and its metabolites in SLE patients with renal impairment who newly started HCQ at a daily dose of 300 mg based on an ideal body weight dosage of 6.5 mg/kg. Population PK analysis was performed using a non-linear mixed-effects model.
In total, 219 samples from 21 patients were analysed. The PK of HCQ in blood after single and multiple oral administrations followed the two-compartment model. At steady state, the concentration ratio of HCQ to each metabolite was HCQ:desethylhydroxychloroquine:desethylchloroquine:bisdesethylchloroquine = 1:0.28:0.1:0.06. The HCQ concentration correlated positively with that of each metabolite. The estimated values (relative standard error) of the population PK parameters were the total clearance at 110 l/h (31%) and a central volume of distribution of 398 l (19%). Co-administration of prednisolone and age, but not renal impairment, were factors affecting the total clearance of HCQ.
From the PK perspective, a dosage reduction is unnecessary in SLE patients with impaired renal function.
对于有肾功能损害的系统性红斑狼疮（SLE）患者，建议减少羟氯喹（HCQ）的剂量，但尚未对有肾功能损害的患者进行药代动力学（PK）研究。
我们对新开始以 6.5mg/kg 理想体重剂量每天 300mg 的 HCQ 治疗的有肾功能损害的 SLE 患者进行了单次和多次 HCQ 及其代谢物的 PK 研究。采用非线性混合效应模型进行群体 PK 分析。
共分析了 21 名患者的 219 个样本。单次和多次口服给药后，HCQ 在血液中的 PK 符合二室模型。在稳态时，HCQ 与各代谢物的浓度比为 HCQ：去乙基羟氯喹：去乙基氯喹：双去乙基氯喹=1:0.28:0.1:0.06。HCQ 浓度与各代谢物浓度呈正相关。群体 PK 参数的估计值（相对标准误差）为总清除率为 110l/h（31%），中央分布容积为 398l（19%）。泼尼松龙和年龄的共同给药，但不是肾功能损害，是影响 HCQ 总清除率的因素。
从 PK 角度来看，肾功能损害的 SLE 患者不需要减少剂量。
