Which antimalarial drug acts by inhibiting the cytochrome P450 enzyme CYP2D6, leading to significant drug interactions?

Explanation

## Mefloquine and CYP2D6 Inhibition **Key Point:** Mefloquine is a known moderate inhibitor of the cytochrome P450 enzyme CYP2D6, which is responsible for metabolizing a wide range of drugs including antiarrhythmics, beta-blockers, tricyclic antidepressants, and opioids (e.g., codeine). ### Mechanism of Drug Interaction **High-Yield:** By inhibiting CYP2D6, mefloquine reduces the metabolic clearance of co-administered CYP2D6 substrates, leading to elevated plasma concentrations and increased risk of toxicity. This is particularly relevant in patients receiving: - **Antiarrhythmics** (e.g., flecainide, propafenone) - **Beta-blockers** (e.g., metoprolol, carvedilol) - **Tricyclic antidepressants** (e.g., amitriptyline) - **Opioids** (e.g., codeine → reduced conversion to morphine) ### Comparison with Other Antimalarials | Drug | CYP450 Interaction | Clinical Relevance | |------|-------------------|--------------------| | Mefloquine | CYP2D6 inhibitor (moderate) | Significant drug interactions | | Quinine | Primarily CYP3A4 substrate; weak CYP2D6 effects | Less prominent CYP2D6 inhibition | | Artemether | CYP3A4 inducer/substrate | Interactions via CYP3A4, not CYP2D6 | | Atovaquone-proguanil | Minimal CYP450 interaction | Well-tolerated combination | **Clinical Pearl:** Mefloquine's CYP2D6 inhibition is a well-documented pharmacokinetic interaction highlighted in standard pharmacology references (KD Tripathi, Goodman & Gilman). This is distinct from its primary antimalarial mechanism (interference with heme detoxification in the parasite). **Warning:** Do not confuse mefloquine's CYP2D6 inhibitory profile with quinine, which is primarily a CYP3A4 substrate and has a different interaction profile. Mefloquine is the antimalarial most consistently associated with CYP2D6 inhibition in pharmacology curricula. *Reference: KD Tripathi – Essentials of Medical Pharmacology, 8th edition; Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th edition.*