Table 2.

Comparative pharmacokinetic properties of triazoles (Sabo and Abdel-Rahman 2000; Jeu et al 2003; Boucher et al 2004; Herbrecht 2004; Sadaba et al 2004; Klasko 2005)

	Voriconazole	Itraconazole	Fluconazole
Cmax (mg/L)	0.9–2.5	0.2–1.1	2
tmax (h)	1–2	3–4	1–3
	Oral: suggestive of saturable first-pass metabolism.
AUC (μg × h/mL)	Oral 19.86–50.32	Oral 22.6	Oral 10.5–15
Bioavailability (%)	90–96	55a	93
Effects of food	Cmax reduced by 34%. AUC reduced by 24%. Tablets should be taken on an empty stomach.	Capsules enhanced absorption. Oral solution decreased bioavailability, so it should not be administered with food.	None
Protein binding (%)	51–67	99	11–12
Vd (L/kg)	2–4.6	10–11	0.7–1.2
Metabolism	Hepatic, by isoenzymes CYP2C19, CYP2C9, and CYP3A4, primarily via N-oxidation.	Hepatic, by CYP isoenzymes.	Hepatic, by CYP isoenzymes.
	N-oxide metabolite inactive (72%).
Excretion	Renal <2% UD and 80%–83% metabolite form. Bile primarily as metabolites.	Renal <1% UD	Renal 80% UD
t1/2 (h)	6	24	31
Hemodialysis	Not dialyzable	Not dialyzable	Yes
	A 4-hour hemodialysis session does not remove a sufficient amount voriconazole to warrant dose adjustment.		Hemodyalisis for 3 hours decreases plasma levels by approximately 50%.

Abbreviations: C_max, maximum concentration; t_max, time to peak concentration (steady state); AUC, area under the curve; V_d, volume of distribution; t_1/2, elimination half-life; UD, unchanged drug.

Note: ^aVariability is a function of prandial state (capsule absorption is pH dependent) and oral formulation.