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Author: Admin | 2025-04-28
Narrow safety range or is dependent on only one enzyme for metabolism. Consider the following scenario: A 35-year-old white woman with panic disorder was treated with paroxetine (Paxil). She developed unrelated hypertension, for which the physician prescribed 50 mg daily of extended-release metoprolol (Toprol XL). The patient became symptomatically orthostatic after a few days and presented to the emergency department. In this example, metoprolol, which is metabolized solely by CYP2D6, was present in higher serum levels in the patient because of the use of paroxetine. Peak serum levels of simvastatin (Zocor), which is metabolized solely by CYP3A4, also can increase by many times in patients who are poor metabolizers or with the addition of a potent inhibitor (e.g., verapamil [Calan], nefazodone [Serzone; brand not available in the United States]), increasing the risk of myopathy and rhabdomyolysis at usual doses.30 Some drugs, such as tramadol or losartan (Cozaar), are not therapeutic until they are metabolized to active compounds. These medications, known as prodrugs, may cause an exaggerated therapeutic effect or adverse effect when a CYP450 inducer is added. Conversely, if a CYP450 inhibitor is combined with a prodrug, or a person is a poor metabolizer of a prodrug, therapeutic failure is likely to result because of little or no production of the active drug.31,32 Genotype Testing Genotyping for CYP450 polymorphism has primarily been used for research purposes or clinical drug trials. Recently, the FDA approved the first genotype test designed for use by physicians to guide the selection of medications metabolized
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