TABLE 3.

Summary of voriconazole pharmacokinetic parameters in pediatric clinical studies and comparison with model predicted values.

CYP2C19 genotype	Dose (mg/kg)	Route	Male (%)	Age in years (age range group)	Pharmacokinetic parameters	Predicted	Observed	Pre/obs ratio	References
58% NM + 42% IM	6 bid d1	i.v. (120)	75	3.7 (2–6)	AUCτ	11.49	11.77	0.98	Walsh et al. (2010)
	4 bid d2-d4	i.v. (80)			Cmax	3.33	3.35	0.99
	6 bid d5-d8	i.v. (120)	75	3.7 (2–6)	AUCτ	20.82	21.93	0.95
					Cmax	3.92	4.69	0.83
73% NM + 27% IM	6 bid d1	i.v. (120)	75	8.7 (6–12)	AUCτ	19.78	11.95	1.66
	4 bid d2-d4	i.v. (80)			Cmax	4.06	3.07	1.32
	6 bid d5-d8	i.v. (120)	75	8.7 (6–12)	AUCτ	36.83	24.05	1.53
					Cmax	6.19	4.01	1.54
75% NM + 17% IM + 8% PM	6 bid d1-d4	i.v. (120)	45.8	2.8 (2–6)	AUCτ	22.39	18.22	1.23
					Cmax	4.85	4.61	1.05
	8 bid d5-d8	i.v. (160)	45.8	2.8 (2–6)	AUCτ	33.84	25.57	1.32
					Cmax	6.00	4.80	1.25
NM	6 bid d1-d4	i.v. (120)	45.8	8.1 (6–12)	AUCτ	26.57	16.23	1.64
					Cmax	5.25	3.99	1.32
	8 bid d5-d8	i.v. (160)	45.8	8.1 (6–12)	AUCτ	41.30	34.68	1.19
					Cmax	6.65	6.92	0.96
NM	9 bid d1	i.v. (180)	42.9	9.2 (3–14)	AUCτ	28.87	36.0	0.80	Mori et al. (2015)
	8 bid d2-d7	i.v. (160)			Cmax	5.42	5.32	1.02
IM	9 bid d1	i.v. (180)	42.9	9.2 (3–14)	AUCτ	58.09	56.4	1.13
	8 bid d2-d7	i.v. (160)			Cmax	8.01	8.12	0.99
PM	9 bid d1	i.v. (180)	42.9	9.2 (3–14)	AUCτ	115	128	0.90
	8 bid d2-d7	i.v. (160)			Cmax	12.78	15.70	0.81

bid, twice daily; d, day; i.v., intravenously; Obs, observed value from clinical studies; Pre, predicted value from PBPK model; NM, normal metabolizer; IM, intermediate metabolizer; PM, poor metabolizer; AUC_τ, area under the concentration-time curve within the dosing interval; C_max, maximum concentration.