The pharmacokinetics of metformin in patients receiving intermittent haemodialysis

• Published in: British journal of clinical pharmacology Vol. 86; no. 7; pp. 1430 - 1443
• Main Authors: Sinnappah, Klarissa A., Kuan, Isabelle H.S., Thynne, Tilenka R.J., Doogue, Matthew P., Wright, Daniel F.B.
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01-07-2020
• Subjects: haemodialysis; Humans; Metformin; NONMEM; pharmacokinetics; Renal Dialysis; Short Report; haemodialysis; pharmacokinetics; metformin; NONMEM
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/bcp.14244

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−1 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−1.