Pharmacokinetics (ADME principles) — MCQs

A 42-year-old man with HIV on antiretroviral therapy (ritonavir-boosted darunavir) develops depression and is prescribed St. John's Wort by a naturopath. His HIV viral load, previously undetectable, rises to 50,000 copies/mL after 3 weeks. He reports perfect medication adherence. Drug levels show subtherapeutic protease inhibitor concentrations despite ritonavir boosting. Evaluate the pharmacokinetic mechanisms and implications of this interaction.

A 58-year-old woman with metastatic breast cancer is enrolled in a trial of a novel oral chemotherapy agent. Pharmacokinetic studies show the drug has 60% bioavailability, is 95% protein-bound, undergoes extensive CYP3A4 metabolism, and has active metabolites. She develops progressive disease at standard dosing. Genetic testing reveals she is a CYP3A4 ultra-rapid metabolizer. She also has mild hypoalbuminemia (3.0 g/dL). Evaluate the most appropriate pharmacokinetic-guided intervention to optimize therapy.

A 65-year-old man with hepatocellular carcinoma and Child-Pugh class C cirrhosis develops severe pain. Morphine 5 mg IV provides minimal relief, but he develops profound sedation lasting 8 hours. Repeat dosing causes respiratory depression. Meanwhile, a similar patient with normal liver function tolerates 10 mg IV morphine well with good pain control and normal alertness after 3 hours. Evaluate the pharmacokinetic and pharmacodynamic factors explaining these contrasting responses.

A 50-year-old man with tuberculosis is started on rifampin. He has been stable on warfarin 5 mg daily for atrial fibrillation with an INR of 2.5. After 10 days of rifampin, his INR drops to 1.2 despite continued warfarin compliance. The warfarin dose is increased to 12 mg daily to achieve therapeutic INR. Three months later, TB treatment is completed and rifampin is discontinued. Analyze what pharmacokinetic changes will occur and predict the management needed.

A 28-year-old woman with depression is taking fluoxetine 40 mg daily with good symptom control. She develops a fungal infection and is prescribed itraconazole. One week later, she presents with tremor, agitation, confusion, and hyperreflexia. Temperature is 38.9°C (102°F). Analyze the pharmacokinetic mechanism underlying this clinical presentation.

A 72-year-old man with chronic kidney disease (GFR 25 mL/min/1.73m²) develops acute pain from herpes zoster. He is prescribed gabapentin 300 mg three times daily. After 5 days, he presents with severe drowsiness, confusion, and myoclonus. Serum gabapentin level is markedly elevated. Analyze the pharmacokinetic alterations that led to this presentation.

A 55-year-old man with newly diagnosed hypertension is started on lisinopril 10 mg daily. His blood pressure is 165/95 mmHg. He has a history of gastroesophageal reflux and takes omeprazole. His BMI is 42 kg/m². After 4 weeks, his blood pressure remains elevated at 160/92 mmHg. Apply your understanding of drug absorption to identify the most likely explanation.

A 32-year-old pregnant woman at 28 weeks gestation presents with a urinary tract infection. She is prescribed nitrofurantoin. Laboratory values show normal renal function. Two days later, she develops dyspnea and chest tightness. Chest X-ray shows bilateral interstitial infiltrates. Apply pharmacokinetic and pharmacodynamic principles to explain this presentation.

A 45-year-old woman with severe pneumonia is prescribed gentamicin. Her serum creatinine is 0.9 mg/dL and creatinine clearance is 95 mL/min. Laboratory monitoring shows a trough level of 3.2 μg/mL (therapeutic range: <2 μg/mL). Apply pharmacokinetic principles to determine the most appropriate management.

A 68-year-old man with atrial fibrillation is started on warfarin therapy. He also takes phenytoin for seizure disorder. After 2 weeks, his INR remains subtherapeutic at 1.3 despite increasing warfarin doses. The patient reports compliance with both medications. Apply your knowledge of pharmacokinetics to explain this drug interaction.