Tacrolimus absorption is lower when co-administered with the potassium binder sodium zirconium cyclosilicate and should be given before or after the potassium binder, according to investigators. The binder does not affect cyclosporin absorption.
Both tacrolimus and cyclosporine are immunosuppressants that can cause hyperkalemia and may be prescribed along with sodium zirconium cyclosilicate.
In a phase 1 study, investigators randomly assigned 31 healthy adults (aged 18 to 50 years) to receive a single dose of immediate-release tacrolimus 5 mg with or without sodium zirconium cyclosilicate 15 g. After a washout period, patients were switched to cyclosporine.
Tacrolimus exposure was reduced when taken concurrently with sodium zirconium cyclosilicate versus alone, Mats Någård, PhD, Senior Group Director of Clinical Pharmacology at AstraZeneca, in Gaithersburg, Maryland, and colleagues reported in Clinical Kidney Journal. The maximum blood concentration (Cmax geometric mean ratio) was 71.10% compared with an area under the concentration-time curve (AUCinf) from time zero to infinity of 62.91%.
To maintain efficacy, tacrolimus should be administered 2 or more hours before or after sodium zirconium cyclosilicate, according to Dr Någård’s team. Tacrolimus’ absorption was reduced, likely due to the potassium binder transiently increasing gastric pH. Sodium zirconium cyclosilicate captures potassium ions in exchange for sodium and hydrogen ions in the gastrointestinal tract, thereby decreasing serum potassium levels.
Investigators also randomly assigned a second cohort of 31 healthy adults to receive a single dose of cyclosporin 100 mg with or without sodium zirconium cyclosilicate 15 g. Patients then crossed over to receive the alternate treatment after washout.
Cyclosporin exposure did not change with sodium zirconium cyclosilicate coadministration, the investigators reported. Cmax geometric mean ratio was 102.9% compared with an AUCinf of 97.23%.
The safety and tolerability of the immunosuppressants tacrolimus and cyclosporin did not change with sodium zirconium cyclosilicate coadministration, the investigators reported.
Disclosure: This research was supported by AstraZeneca. Please see the original reference for a full list of disclosures.
Någård M, Choudhury N, Al-Shurbaji A, Lisovskaja V, Mackillop N. A Phase 1, open-label, crossover study evaluating the effect of a single dose of sodium zirconium cyclosilicate on the pharmacokinetics of tacrolimus and cyclosporine. Clinical Kidney J. Published online September 13, 2022. doi:10.1093/ckj/sfac205