医学
羟基氯喹
药代动力学
分配量
内科学
肾功能
人口
系统性红斑狼疮
泼尼松龙
代谢物
红斑狼疮
药理学
胃肠病学
免疫学
疾病
传染病(医学专业)
抗体
环境卫生
2019年冠状病毒病(COVID-19)
作者
Mikiko Shimizu,Sumito Furudate,Yusuke Nagai,Kota Shimada,Masato Ohshima,Keigo Setoguchi,Masayuki Hashiguchi,Naoto Yokogawa
摘要
ABSTRACT Objectives 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. Methods 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. Results 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. Conclusions From the PK perspective, a dosage reduction is unnecessary in SLE patients with impaired renal function.
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