Pharmacokinetics Practice Test

A 48-year-old man with cirrhosis from nonalcoholic steatohepatitis is started on oral propranolol for portal hypertension prophylaxis. He develops lightheadedness and bradycardia after the first few doses. Exam: HR 48/min, BP 92/54 mm Hg. Labs: total bilirubin 3.1 mg/dL, albumin 2.8 g/dL, INR 1.7, creatinine 1.0 mg/dL. Propranolol undergoes extensive first-pass hepatic metabolism with low oral bioavailability in healthy adults; Vd $\approx 4\ \text{L/kg}$ and half-life $\approx 3$–6 hours. In cirrhosis, first-pass metabolism is reduced, increasing systemic exposure after oral dosing. Which of the following best describes how the pharmacokinetics of propranolol is altered in this patient?

A 60-year-old woman with primary biliary cholangitis and cirrhosis is started on oral morphine for severe pain. Within 24 hours she becomes increasingly sedated with shallow respirations. Exam: RR 8/min, pinpoint pupils. Labs: total bilirubin 6.0 mg/dL, albumin 2.4 g/dL, INR 2.0, creatinine 0.9 mg/dL. Morphine has significant first-pass metabolism; hepatic clearance contributes substantially to elimination, and normal half-life is ~2–3 hours. The team reviews that impaired hepatic metabolism can increase bioavailability and reduce clearance, leading to higher plasma concentrations at a given dose. Which pharmacokinetic parameter is most affected by liver disease in this patient?