# Investigation of Renal Tissue Deposition of the Calcineurin Inhibitors Voclosporin, Cyclosporine and Tacrolimus Using MALDI-MSI Imaging

## TL;DR

This study uses imaging mass spectrometry to compare how three calcineurin inhibitors distribute and are retained in the kidneys of mice, revealing distinct patterns that may explain differences in their safety profiles.

## Contribution

The study provides the first MALDI-MSI imaging comparison of renal tissue distribution and retention of voclosporin, tacrolimus, and cyclosporine in mice.

## Key findings

- Voclosporin showed rapid excretion with minimal renal retention after 2 hours.
- Cyclosporine A exhibited persistent renal distribution for up to 4 hours.
- Tacrolimus was retained in the renal medulla for up to 7 hours.

## Abstract

Calcineurin inhibitors (CNIs) are immunosuppressive agents that inhibit calcineurin (CN) and are recommended for the treatment of lupus nephritis (LN). In clinical trials, differences in the safety profiles of CNIs have been observed. Emerging data suggests that small molecule therapeutics may be differentially distributed and retained within organ tissues, potentially explaining these safety profile disparities.

This study investigated the renal distribution and retention of the CNIs voclosporin (VCS), tacrolimus (TAC), and cyclosporine A (CSA) in CD-1 mice using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-MSI).

Distinct patterns of the distribution and retention of these compounds were observed. VCS showed a moderate cortical distribution, peaking between 15- and 30 min post administration, and was then rapidly excreted with minimal renal retention observed by 2 h post-dosing. In contrast, CSA exhibited a diffuse, persistent distribution in renal structures for up to 4 h post-dosing. TAC showed a diffuse distribution pattern, with retention observed in the renal medulla for up to 7 h post-dosing.

These data indicate that CNIs display different renal handling profiles. The shorter duration of renal retention of VCS demonstrated in the healthy mice indicates a differentiated profile compared to the other CNIs. Further research on the body-wide tissue distribution and renal handling of TAC, VCS and CSA in humans will aid in delineating the distinct clinical profiles of CNIs and optimize their use in treating immune disorders.

The online version contains supplementary material available at 10.1007/s11095-025-03943-y.