# Optimization of Ibuprofen Route and Dosage to Enhance Protein-Bound Uremic Toxin Clearance During Hemodialysis

## TL;DR

This study finds that administering ibuprofen through the arterial line during dialysis improves the removal of harmful toxins bound to proteins in the blood.

## Contribution

The study identifies the optimal dose and route of ibuprofen administration to enhance toxin clearance during hemodialysis.

## Key findings

- Arterial-line ibuprofen administration improves the clearance of indoxyl sulphate and p-cresyl sulphate during hemodialysis.
- Higher doses of ibuprofen (800 mg) administered via the arterial line result in greater toxin removal compared to lower doses.
- Prolonged low-dose ibuprofen infusion may reduce systemic exposure and toxicity risk while maintaining effective toxin clearance.

## Abstract

Protein-bound uremic toxins (PBUT), particularly indoxyl sulphate (IS) and p-cresyl sulphate (pCS), are poorly removed by conventional haemodialysis because of their strong albumin binding. These toxins are associated with cardiovascular morbidity and mortality in haemodialysis patients. Displacer molecules such as ibuprofen enhance PBUT clearance by competing for albumin-binding sites, but the optimal dose and route of administration remain unclear. The aim of this study was to evaluate the effect of different ibuprofen doses, infusion durations, and routes of administration on the removal of IS and pCS during on-line hemodiafiltration (OL-HDF). In this prospective, single-centre, crossover study, 21 chronic haemodialysis patients receiving intradialytic analgesia underwent nine OL-HDF sessions. Ibuprofen was administered at two doses (400 or 800 mg) either in the arterial pre-filter line (infusion over 1 h, 2 h, or 3 h) or in the venous post-filter line (30 min). Reduction ratios (RR) of total IS and pCS were determined by LC-MS and corrected for haemoconcentration. Statistical analysis included repeated-measures ANOVA with post-hoc testing. Baseline RR for IS and pCS were 53.7 ± 9.9% and 47.1 ± 10.9%, respectively. The highest RR was achieved with 800 mg ibuprofen infused via the arterial line over 2 h (IS: 60.8 ± 8.6%; pCS: 57.8 ± 9.7%). All arterial-line 800 mg regimens and the 3-h 400 mg infusion significantly improved pCS clearance versus baseline; IS clearance improved significantly only with arterial-line 800 mg regimens and with the 400 mg 3-h infusion. Infusion rate (1–3 h) had no significant effect on RR within the same dose group. Pain scores decreased significantly after dialysis regardless of ibuprofen regimen. Arterial-line administration of ibuprofen enhances total IS and pCS removal during OL-HDF, with higher doses yielding greater clearance. Prolonged low-dose infusion appears similarly effective for pCS and may reduce systemic exposure, potentially lowering toxicity risk. These findings support the arterial line as the preferred route for displacer administration in clinical practice.