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Background <p>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.</p> Methods <p>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).</p> Results <p>Distinct patterns of the distribution and retention of these compounds were observed. VCS showed a moderate cortical distribution, peaking between 15- and 30&#xa0;min post administration, and was then rapidly excreted with minimal renal retention observed by 2&#xa0;h post-dosing. In contrast, CSA exhibited a diffuse, persistent distribution in renal structures for up to 4&#xa0;h post-dosing. TAC showed a diffuse distribution pattern, with retention observed in the renal medulla for up to 7&#xa0;h post-dosing.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月8日

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  • Simon Zhou,
  • Krishani Kumari Rajanayake,
  • Miao He,
  • Bo Wen,
  • Ankhbayar Lkhagva,
  • Ernie Yap,
  • Duxin Sun,
  • Jennifer Cross,
  • Kory Engelke,
  • Robert B. Huizinga

摘要

Background

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.

Methods

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).

Results

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.

Conclusions

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.