Which of the following is an example of a pharmacokinetic related ADR?

• A. Drugs that increase renal clearance leading to loss of efficacy.
• B. Reduced elimination in older patients, drugs competing for plasma protein binding, or metabolic enzyme inhibition, producing increased concentration that causes adverse effects.
• C. Co-administration of two drugs that share the same receptor/target or signaling pathway.
• D. Ginkgo biloba with NSAIDs increases bleeding risk.

Answer: (B)

Pharmacokinetic adverse drug reactions happen when changes in how the body handles a drug alter its exposure and lead to toxicity or other problems. The best example is when elimination is reduced—due to aging, competition for plasma protein binding, or metabolic enzyme inhibition—because that raises the drug’s plasma concentration (higher free drug, longer half-life, greater AUC), making adverse effects more likely. This ties drug levels directly to harm, which is the essence of a PK-related ADR.

In contrast, interactions that involve the drug’s effect on targets or pathways (pharmacodynamics) don’t primarily arise from changed drug levels. For example, two drugs acting at the same receptor or pathway are PD interactions, not PK. And combining a herb with NSAIDs that increases bleeding risk is more about additive bleeding risk from PD effects (platelet function, inflammatory pathways) rather than altered drug concentration. Increasing renal clearance leading to loss of efficacy describes underexposure, not toxicity, so it doesn’t illustrate an ADR driven by increased exposure.