Table 3.

Hepatic adverse events (unrelated to study drug) versus corresponding observed voriconazole exposure parameters in children^a

Subject	Hepatic adverse event(s) (unrelated to study drug)	AE onset study day	Treatment period	AUC0-12 (μg·h/ml)	Cmax (μg/ml)	Cmin (μg/ml)
5	Hyperbilirubinemia	9	IV	14.9	4.09	0.18
6	Hyperbilirubinemia	12	IV	60.8	7.72	3.57
6	Hepatomegaly	18	Oral	13.0	1.93	0.27
7	Hyperbilirubinemia	12	IV	7.33	1.82	0.23
10	Hepatomegaly, hyperbilirubinemia	8	IV	24.1	3.73	0.25
14	Hyperbilirubinaemia	19	IV	5.02	1.63	0.07
16	Increased GGT	11	IV	15.1	4.20	0.11
17	Increased blood lactate dehydrogenase, increased GGT	6	IV	34.3	5.81	1.33
18	Increased hepatic enzyme	4	IV	24.3	5.26	0.55
21	Decreased hepatic enzyme	9	IV	26.9	4.04	0.97
23	Hepatomegaly, increased ALT	29	IV	7.32	2.44	0.24
25	Increased ALT, AST, and GGT; hepatosplenomegaly	18	IV	16.1	3.67	0.49
27	Increased AST	49	Oral	16.3	2.86	0.53
28	Increased GGT	19	Oral	60.6	8.44	1.83
29	Increased ALT, AST, and GGT	13	Oral	69.6	10.7	2.23
31	Increased ALT and AST	4	IV	7.74	1.48	0.16
33	Hyperbilirubinemia, increased AST	17	Oral	203	18.0	12.8
34	Increased AST and GGT, hyperbilirubinemia	37	Oral	21.7	3.58	0.89
35	Hyperbilirubinemia	5	IV	6.47	2.08	0.06

^aAE, adverse event; GGT, gamma glutamyltransferase; ALT, alanine aminotransferase; AST, aspartate aminotransferase. Two subjects with hepatic events were excluded due to lack of corresponding exposure parameters. Steady-state IV and oral voriconazole exposures were used as the estimates for AEs that occurred on nonpharmacokinetic days.