Triamterene kinetics and dynamics in cirrhosis

Area of Science:

• Pharmacology
• Hepatology
• Drug Metabolism

Background:

• Triamterene undergoes extensive liver metabolism and first-pass elimination.
• Cirrhosis is known to affect drug metabolism and disposition.

Purpose of the Study:

• To investigate the pharmacokinetic differences of triamterene in healthy controls versus patients with cirrhosis and ascites.
• To assess the impact of cirrhosis on triamterene metabolism and its major metabolite, p-hydroxy-triamterene sulfate (OH-T-S).

Main Methods:

• Utilized a specific and sensitive High-Performance Liquid Chromatography (HPLC) assay.
• Measured plasma concentrations of triamterene and OH-T-S.
• Quantified urinary recovery of OH-T-S.

Main Results:

• Apparent oral clearance of triamterene was reduced by 92% in cirrhotic patients compared to controls.
• The ratio of metabolite to parent drug (AUCOH-T-S/AUCtriamterene) decreased significantly in cirrhosis.
• Urinary recovery of OH-T-S dropped from 45% in controls to 15% in cirrhotic patients.

Conclusions:

• Cirrhosis markedly impairs triamterene disposition, characterized by reduced oral clearance and altered metabolism.
• The impaired drug metabolism in cirrhosis prolongs the natriuretic effect of triamterene.
• These findings highlight the significant impact of liver disease on drugs with substantial first-pass metabolism.