Abstract
BackgroundVoriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP 3A4. Drug-drug interactions and genetic polymorphisms modulate their activities.Case presentationA 35-year old African female patient with resistant HIV and a cerebral mass of unknown origin was treated with voriconazole for a suspicion of disseminated Aspergillosis infection. Voriconazole trough concentrations (C0) were within target range while the patient was under esomeprazole, a CYP2C19 inhibitor. Phenotyping showed decreased CYP2C19 activity, whereas genotyping showed a variant allele associated with increased enzyme activity. The patient was switched to ranitidine because of the introduction of atazanavir. CYP3A4 inhibition by atazanavir combined with uninhibited CYP2C19 activity resulted in subtherapeutic voriconazole C0. The reintroduction of esomeprazole allowed restoring voriconazole C0 back to target range.ConclusionThe integration of drug-drug interactions and pharmacogenetics data is crucial to interpret drug concentrations correctly, thus preventing suboptimal exposure to voriconazole.
Highlights
Voriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP 3A4
[1] Voriconazole is mainly metabolized by cytochrome P450 (CYP) 2C19 and 3A4, [2] and its clearance is modulated by drug – drug interactions (DDI) [3,4] and genetic polymorphisms [5,6,7]
We report a case of multiple DDI in a patient with an increased CYP2C19 activity that led to variations in voriconazole trough concentrations (C0)
Summary
Voriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP 3A4. Drug-drug interactions and genetic polymorphisms modulate their activities.Case presentation: A 35-year old African female patient with resistant HIV and a cerebral mass of unknown origin was treated with voriconazole for a suspicion of disseminated Aspergillosis infection. [1] Voriconazole is mainly metabolized by cytochrome P450 (CYP) 2C19 and 3A4, [2] and its clearance is modulated by drug – drug interactions (DDI) [3,4] and genetic polymorphisms [5,6,7]. We report a case of multiple DDI in a patient with an increased CYP2C19 activity that led to variations in voriconazole trough concentrations (C0). Voriconazole C0 reached and stayed within the targeted range with the use of inhibitors of CYP2C19 and CYP3A4.
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