Voriconazole differs from fluconazole in its spectrum and pharmacokinetics. Which feature is unique to voriconazole among triazoles?
- A It has activity against Candida glabrata and Candida krusei (fluconazole-resistant species) and Aspergillus, plus saturable (non-linear) pharmacokinetics at therapeutic doses ✓
- B It is the only triazole with activity against Zygomycetes (mucormycosis)
- C It is renally eliminated and requires dose adjustment for CrCl <50 mL/min
- D It acts by inhibiting 14α-demethylase and squalene epoxidase simultaneously
Correct answer: A. It has activity against Candida glabrata and Candida krusei (fluconazole-resistant species) and Aspergillus, plus saturable (non-linear) pharmacokinetics at therapeutic doses
Explanation
Voriconazole has a broader spectrum than fluconazole covering C. krusei, C. glabrata (often fluconazole-resistant), and importantly Aspergillus species; it is the drug of choice for invasive aspergillosis. Notably, voriconazole exhibits non-linear (saturable) pharmacokinetics because it is both a CYP2C19 substrate and inhibitor — at higher doses autoinhibition results in disproportionately elevated plasma levels, complicating dosing. Zygomycetes (Mucor, Rhizopus) are not covered by voriconazole — posaconazole/isavuconazole are used for mucormycosis.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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