Pharmacokinetics Practice Test

A 70-year-old man with atrial fibrillation is taking oral warfarin (stable INR 2.3). He begins trimethoprim-sulfamethoxazole for a urinary tract infection. Four days later, he presents with epistaxis and gingival bleeding. Labs: INR 6.1, hemoglobin 12.8 g/dL, creatinine 1.0 mg/dL, AST 28 U/L, ALT 24 U/L, albumin 4.1 g/dL. Warfarin is highly albumin-bound and primarily cleared by hepatic metabolism; its half-life is ~36 hours. The clinician suspects a drug-drug interaction affecting clearance and/or free fraction. Which of the following best describes how the pharmacokinetics of warfarin 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?