Pharmacokinetics of Colistin in Critically-ill Patients With AKI Who Receive SLED

Summary

Colistin was developed in the 1960s and preliminary pharmacokinetic studies were performed at that time. Dosing recommendations, on the basis of these pharmacokinetic studies, are listed in the drug's product information. However, there are no optimal dosing recommendations for patients with acute kidney injury who receive sustained low-efficiency dialysis. Furthermore, the science of antibiotic dosing ("pharmacodynamics") has changed significantly since the 1960s and it is quite possible that the dosing recommendations listed in the product information are not optimal. Furthermore, even though physicians refer to "colistin" administration, the only intravenous form of the drug is colistin methanesulfonate (CMS). CMS is converted in the body to colistin. Both CMS and colistin have different pharmacokinetic and antimicrobial activities. For this reason, we, the investigators at the Mahidol university, are performing a pharmacokinetic study of the intravenous CMS/colistin in patients requiring sustained low-efficiency dialysis. Plasma concentrations will be determined around a CMS/colistin dose once the drug has reached steady state. Microbiologic and clinical endpoints will be determined and will be correlated with these concentrations. The measurement of CMS and colistin levels will be determined by a laboratory in Australia.

Timeline

Start

2021-10-18

Primary completion

2022-10-31

Completion

2022-10-31

Publications

• Background Nation RL, Garonzik SM, Thamlikitkul V, Giamarellos-Bourboulis EJ, Forrest A, Paterson DL, Li J, Silveira FP. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis. 2017 Mar 1;64(5):565-571. doi: 10.1093/cid/ciw839. Epub 2016 Dec 23.
• Background Jitmuang A, Nation RL, Koomanachai P, Chen G, Lee HJ, Wasuwattakul S, Sritippayawan S, Li J, Thamlikitkul V, Landersdorfer CB. Extracorporeal clearance of colistin methanesulphonate and formed colistin in end-stage renal disease patients receiving intermittent haemodialysis: implications for dosing. J Antimicrob Chemother. 2015;70(6):1804-11. doi: 10.1093/jac/dkv031. Epub 2015 Feb 18.

Drugs

Indications