ArticleToxicology reports2025
Potential amelioration of liver function by low-dose tolvaptan in heart failure patients.
Article in Toxicology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Aim: This study aimed to evaluate the relationships between the pharmacokinetics of tolvaptan and its metabolites (DM-4103 and DM-4107) and liver injury in heart failure patients, using relevant laboratory test values and markers of hepatocyte injury and biliary cholestasis. Method: The plasma concentrations of tolvaptan, DM-4103, and DM-4107 were determined using LC-MS/MS in 51 Japanese heart failure patients. The relationships between the concentrations and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), AST, and ALT were assessed. K18 and glutamate dehydrogenase as a marker of liver injury and CP-I and CP-III as indicators of OATP activity were also determined. Results: The median concentrations of tolvaptan, DM-4103, and DM-4107 were 16.2, 287, and 38.0 ng/mL, respectively. AST, ALT, and T-Bil were significantly decreased after tolvaptan administration. They were negatively correlated with tolvaptan concentration. AST was also negatively correlated with DM-4107 concentration. CP-III was positively correlated with DM-4103 concentration; however, CP-I was negatively correlated with DM-4103 concentration. K18 and glutamate dehydrogenase were not correlated with tolvaptan concentration. Conclusion: Low-dose tolvaptan did not cause liver injury. Pharmacokinetics of tolvaptan may be associated with potential amelioration of liver function in heart failure patients.
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