TABLE 1

In vitro-in vivo relationship of voriconazole clearance in children and adults

Group	Subject	Age	K_m^a	V_max^a	Scaling Factor	Intrinsic Clearance^b	In Vivo Clearance
Group	Subject	Age	K_m^a	V_max^a	Scaling Factor	Intrinsic Clearance^b	Calculated^c	Observed^d
		yr	μM	pmol/min/mg	mg/kg	ml/min/kg	ml/min/kg
Adults	A1	45	8.5 ± 0.9	28.0 ± 0.7	655.7	2.16
	A2	58	8.8 ± 1.1	44.6 ± 2.3	801.4	3.6
	A3	24	9.8 ± 2.3	62.5 ± 1.7	600.0	3.8
	A4	20	8.5 ± 1.0	35.6 ± 0.8	578.6	2.4
	A5	39	15.7 ± 4.3	45.2 ± 3.0	535.7	1.5
	A6	46	4.5 ± 0.6	24.2 ± 0.9	728.6	3.9
			9.3 ± 3.6^e	40.0 ± 13.9^e	650.0 ± 99.8^e	2.9 ± 1.0^e	1.6 ± 0.6^e	2.0^e
Children	C1	2	3.8 ± 0.4	63.0 ± 2.5	900.8	14.9
	C2	4	19.7 ± 2.9	315.5 ± 12.7	786.7	16.2
	C3	8	11.9 ± 1.7	139.1 ± 4.5	844.9	10.7
	C4	2	12.1 ± 1.5	73.1 ± 1.5	705.0	4.3
	C5	4	10.0 ± 1.4	68.8 ± 2.3	1311.1	8.3
	C6	5	8.5 ± 1.6	63.4 ± 2.3	721.1	4.8
			11.0 ± 5.2^e	120.5 ± 99.9^e	878.3 ± 211.3^e	9.9 ± 5.0^e	5.1 ± 2.6^e	6.7^e

↵a The K_m and V_max values for each subject are reported as mean ± S.D.; these values were derived from three determinations of the reaction rate at each substrate concentration.
↵b The (whole body) intrinsic clearance for each subject was calculated from the experimentally determined in vitro intrinsic clearance (V_max/K_m) values using eqs. 1 and 2 (see Materials and Methods).
↵c In vivo clearance is calculated based on in vitro data according to the well stirred model of hepatic disposition that is described by eq. 3 (see Materials and Methods).
↵d Clinically observed clearance values in children and adults were reported by Levêque et al. (2006).
↵e Mean ± S.D.