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Research Article: Pharmacokinetics and Tolerability of Zibotentan in Patients with Concurrent Moderate Renal and Moderate Hepatic Impairment

Date Published: 2023-10-06

Abstract:
Zibotentan, a selective endothelin A receptor antagonist, is in development for chronic liver and kidney disease. The pharmacokinetics (PK) of zibotentan were previously investigated in patients with either renal impairment or hepatic impairment, but the impact of both pathologies on PK was not evaluated. This study evaluated the PK and tolerability of a single oral dose of zibotentan in participants with concurrent moderate renal impairment and moderate hepatic impairment versus control participants.

Introduction:
Liver cirrhosis represents a substantial health burden, with the number of deaths and disability-adjusted life years as well as the proportion of all global deaths due to cirrhosis increasing since 1990 [1]. Liver cirrhosis is initially described as ‘compensated’, which progressively worsens as portal pressure increases and liver function decreases. Clinically significant portal hypertension increases the risk for decompensation events including ascites, variceal bleeding, encephalopathy and associated…

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