Which is an example of a pharmacokinetic drug-drug interaction?

• A. A drug inhibiting a drug transport pump in the intestinal lumen.
• B. Drugs altering the rate of gastric emptying.
• C. Drugs altering the pH of the stomach or intestine, interfering with disintegration, dissolution, and absorption of the drug.
• D. A drug inhibiting or inducing hepatic cytochrome P450 (CYP) enzymes.

Answer: (D)

Pharmacokinetic drug-drug interactions are those that change how the body handles a drug, altering absorption, distribution, metabolism, or excretion so that drug concentrations vary. The most classic example is when a drug inhibits or induces hepatic cytochrome P450 enzymes, because metabolism largely governs clearance and systemic exposure. If another drug inhibits these enzymes, metabolism slows, the drug’s half-life and overall exposure (area under the curve) rise, raising risk of toxicity. If a drug induces these enzymes, metabolism speeds up, exposure falls and the drug may become less effective. This mechanism directly changes the body's ability to clear the drug and is a central, well-recognized source of clinically important interactions that often requires dose adjustments or alternative therapy.

Changes in absorption, such as drug interference with intestinal transporters, slower or faster gastric emptying, or altered stomach/intestinal pH affecting dissolution, are also pharmacokinetic in that they modify concentrations by affecting absorption. However, the hepatic CYP enzyme interaction is the clearest and most impactful example of a pharmacokinetic interaction due to its profound effect on metabolism and clearance.