Physiologically based pharmacokinetic (PBPK) modelling considers hepatic drug extraction. A drug with a high extraction ratio (E > 0.7) given orally would have which set of pharmacokinetic characteristics?

• A Low oral bioavailability due to extensive first-pass effect; clearance primarily rate-limited by hepatic blood flow (not intrinsic clearance) ✓
• B High oral bioavailability; clearance limited by plasma protein binding and intrinsic metabolic capacity
• C High oral bioavailability; clearance unchanged by hepatic blood flow alterations
• D Low oral bioavailability due to poor intestinal absorption; clearance unaffected by cirrhosis

Explanation

The hepatic extraction ratio (E) describes the fraction of drug removed from the blood in a single pass through the liver. High-extraction drugs (E > 0.7, e.g., morphine, lidocaine, propranolol, verapamil) have their hepatic clearance primarily determined by hepatic blood flow (Q_H), not by intrinsic clearance or protein binding — 'flow-limited' drugs. Oral bioavailability is low due to extensive first-pass hepatic extraction. Any condition altering hepatic blood flow (heart failure, liver disease, portal hypertension) significantly changes clearance of high-extraction drugs. Low-extraction drugs (E < 0.3, e.g., warfarin, phenytoin) have clearance limited by free fraction and intrinsic clearance — 'capacity-limited' drugs.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.