Comparative Pharmacology Table
| Parameter | Omeprazole | Diphenhydramine | Pravastatin |
|---|---|---|---|
| Mechanism of Action | Proton pump inhibitor; irreversibly inhibits H+/K+-ATPase in gastric parietal cells, blocking gastric acid secretion | Histamine H1-receptor antagonist with anticholinergic and sedative properties [1,2] | HMG-CoA reductase inhibitor; competitively inhibits cholesterol synthesis in hepatocytes |
| Half-life | 0.5-1 hour (drug); effect lasts 24+ hours due to irreversible binding | 4-6 hours duration of effect [1,2] | 1.5 hours [3] |
| P-glycoprotein Interaction | Substrate and inhibitor of P-gp; inhibits with IC50 of 17.7 μM [4] | Not well-characterized in provided evidence | Not a significant P-gp substrate or inhibitor; pravastatin relies on OATP1B1 transport rather than P-gp [3,5] |
| CYP2D6 Interaction | Inhibitor of CYP2D6 (though primarily metabolized by CYP2C19 and CYP3A4) | Competitive inhibitor of CYP2D6 with Ki ≈11 μM; can cause clinically significant interactions with CYP2D6 substrates like metoprolol [6,7] | No significant CYP2D6 interaction; minimally metabolized, not eliminated via CYP450 enzymes [3] |
| Effect on QT Interval | No significant QT prolongation documented in provided evidence | No significant QT prolongation documented in provided evidence | No significant QT prolongation documented in provided evidence |
| Effect on Cardiac Conduction | No direct cardiac conduction effects; may interact with clopidogrel (CYP2C19 inhibition) but COGENT trial showed no increased cardiovascular events [8,9] | Hypotension reported as adverse effect; modest stimulatory effect on ventilation [1,2] | No direct cardiac conduction effects; safe in hypertensive patients on antihypertensive therapy [10] |
Key Clinical Considerations
Omeprazole's most clinically relevant interaction involves CYP2C19 inhibition affecting clopidogrel metabolism, though the COGENT trial demonstrated no increased cardiovascular events despite pharmacodynamic interactions 8, 9. Omeprazole acts as both substrate and inhibitor of P-glycoprotein 4, which may contribute to drug interactions beyond CYP-mediated pathways.
Diphenhydramine's CYP2D6 inhibition is clinically significant, particularly with narrow therapeutic index drugs like metoprolol, where it decreased clearance twofold and prolonged beta-blocker effects 7. This over-the-counter medication can cause meaningful interactions despite its common use.
Pravastatin stands apart as it is minimally metabolized by CYP450 enzymes and relies primarily on OATP1B1 transport 3. This makes it less susceptible to typical statin drug interactions, though caution remains with OATP1B1 inhibitors like cyclosporine (which increases pravastatin AUC by 282%) 3.