Table 1.
Triazole antifungal agents: Comparison of pharmacokinetic data (modified from [3])
| Parameter | Fluconazole | Itraconazole | Voriconazole | Posaconazole |
|---|---|---|---|---|
| Formulations | I.v. infusion, p.o. capsules, p.o. solution | I.v. infusion (CDx), p.o. capsules, p.o. solution (CDx) | I.v. infusion (CDx), p.o. capsules, PO suspension | p.o. suspension |
| Maintenance dose for antifungal treatment | 400 mg i.v. and p.o.od | 200 mg i.v. and p.o. bid | 4 mg/kg i.v. bid; 200 mg p.o. bid | 400 mg bid |
| Absolute bioavailability (comment) | ≥90% (independent of food and gastric pH) | <55% (capsules dependent on food and gastric pH, in contrast to solution) | <90% (availability decreased by fat-rich foods) | 8%–47% (dose-dependent; availability increased by fat-rich foods) |
| Protein binding | 12% | 99.8% | 58% | 98%–99% |
| Half-life | 27 h | 21–64 h | 6 h | 25 h |
| Elimination | Renal≫faecal; primarily in unchanged form | Faecal≫renal; primarily as metabolites; (ω-1)-hydroxyitraconazole with antifungal activity | Renal≫faecal; primarily as inactive metabolites | Faecal≫renal; extensively in unchanged form |
| Metabolism | No | CYP3A4 | CYP2C19>2C9, 3A4 | UGT1A4 |
| CYP inhibition | CYP2C9>3A4;>2C19 | CYP3A4≫2C9 | CYP3A4, 2C19, >2C9 | CYP3A4 |
CDx: hydroxypropyl-β-cyclodextrin in itraconazole for injection (should not be used in patients with creatinine clearance [CLcr] < 30 ml min−1); β-cyclodextrin-sulfobutylether sodium in voriconazole for injection (should not be used in patients with CLcr < 50 ml min−1). Bid, twice daily; i.v., intravenous; od, once daily; p.o., oral. Table adapted from Lipp HP. Mycoses 2008; 51: 7–18, with permission [3].