Activation of tolvaptan-responsive T-cell clones with the structurally-related mozavaptan

Tolvaptan is an effective drug for the treatment of autosomal dominant polycystic kidney disease, but its use is associated with a significant risk of T-cell-mediated liver injury in a small number of patients. An important clinical conundrum following the contraindication of tolvaptan is whether administration of agents of similar pharmacological action and structure will be tolerated. Herein, we addressed this question through the exposure of tolvaptan-responsive T-cell clones to similar pharmaceutical agents. Whilst lixivaptan and conivaptan did not activate tolvaptan-responsive T-cells, mozavaptan evoked proliferative responses comparable with tolvaptan itself, indicating that there may be collateral immunological intolerance to this compound as a product of sensitization to tolvaptan.

Automated summary

Tolvaptan is effective for treating polycystic kidney disease, but its use carries a risk of T-cell-mediated liver injury. After contraindication, the tolerance of similar drugs with similar pharmacological actions and structures is a clinical challenge. In this study, tolvaptan-responsive T-cell clones were exposed to similar pharmaceutical agents, and it was found that mozavaptan induced a comparable immune response as tolvaptan, suggesting potential immunological intolerance.