The goal of this clinical trial is to learn how liver cirrhosis affects the way the body processes drugs in adults with different stages of liver cirrhosis. This information may help improve drug dosing for people with liver cirrhosis in the future. The main question it aims to answer is:
• How does the severity of liver cirrhosis affect the way the body processes a combination of five drugs, each used to measure the activity of a different liver enzyme?
Researchers will compare participants with mild, moderate, and severe liver cirrhosis to see whether the processing of drugs differs between these groups.
Participants will:
* Fast overnight for 8 hours before receiving the drugs * Have a scan to measure the stiffness of their liver and spleen * Receive a single low dose of five drugs: caffeine, warfarin, esomeprazole, metoprolol, and midazolam * Have blood samples taken before and at several times up to 72 hours after receiving the drugs, including samples for genetic testing and blood clotting checks * Avoid caffeine-containing food and drinks from 48 hours before receiving the drugs until the final blood sample
Age ≥ 18 years
Clinical, radiological and/or histological diagnosis of cirrhosis
Informed consent signed prior to participation in the study
Original MELD score > 30
Estimated creatinine clearance < 30 mL/min, calculated by using the Cockcroft-Gault equation
Known poor metaboliser status for one of the CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A) described in the medical record
Previous clinically relevant adverse reaction or intolerance to one of the drugs in the probe drug cocktail