School of Pharmacy, University of Otago, Dunedin, New Zealand.
Department of Clinical Pharmacology, Flinders Medical Centre and Flinders University, Adelaide, Australia.
Br J Clin Pharmacol. 2020 Jul;86(7):1430-1443. doi: 10.1111/bcp.14244. Epub 2020 Feb 25.
The aims of this study were to characterise the population pharmacokinetics of metformin in patients receiving haemodialysis, and to determine the doses that will maintain median metformin plasma concentrations below 5 mg L for a typical individual. Metformin plasma concentrations from 5 patients receiving thrice weekly intermittent haemodialysis followed by metformin 500 mg postdialysis were fitted to a published pharmacokinetic model. Additional models to describe the dialytic pharmacokinetics of metformin were explored. Doses of 250 and 500 postdialysis were simulated from the model for a typical haemodialysis patient. The published 2-compartment pharmacokinetic model with an additional parameter to describe haemodialysis clearance provided a reasonable fit to the data. Deterministic simulations from the model for a typical individual suggest that metformin doses of 250-500 mg postdialysis and 250 mg given once daily should maintain median metformin plasma concentrations below 5 mg L .
本研究的目的是描述接受血液透析的患者中二甲双胍的群体药代动力学，并确定将中位数二甲双胍血浆浓度维持在 5mg/L 以下的剂量。对接受每周三次间歇性血液透析后接受二甲双胍 500mg 透析后治疗的 5 名患者的二甲双胍血浆浓度进行拟合，以建立已发表的药代动力学模型。探索了描述二甲双胍透析药代动力学的其他模型。根据模型，对典型血液透析患者进行了 250 和 500 次透析后剂量的模拟。具有描述血液透析清除率的附加参数的已发表 2 隔室药代动力学模型对数据提供了合理的拟合。来自模型的典型个体的确定性模拟表明，透析后剂量为 250-500mg 和每日 250mg 应将中位数二甲双胍血浆浓度维持在 5mg/L 以下。
