Table 7.

Multiple dose lapatinib (1,250–1,800 mg) observed and predicted human AUC_τ and subject characteristics

Dose (mg)	Observed AUCτ (nM × h)	Predicted AUCτ (nM × h)	AUCτ PE%c	Subjects	Food	Bilirubind	ASTd	ALTd	Age (years)e	Reference
1,250	62,300 (40,271–96,376)a	30,631	−50.8	Cancer	Not fasted	≤1.5 mg/dL	≤2.0× ULN	≤2.0× ULN	58.3 (2–79)	[7]
1,250	68,840 (50,425–94,138)b	30,631	−55.5	Cancer	Not fasted	Significant dysfunction excluded			58 (34–78)	[8]
1,250	24,438 (11,789–50,941)b	30,631	25.3	Cancer	Fasted	≤1.5 mg/dL	≤2.0× ULN	≤2.0× ULN	59 (19–74)	[10]
1,250	40,099 (24,954–64,193)b	30,631	−23.6	Cancer	Not fasted	≤2.0× ULN	≤5.0× ULN	≤5.0× ULN	57.5 (33–74)	[12]
1,500	46,639 (32,699–66,430)b	36,757	−21.2	Cancer	Not fasted	≤1.5 mg/dL	≤2.0× ULN	≤2.0× ULN	59.5 (39–73)	[6]
1,500	54,900 (29,601–101,833)b	36,757	−33.0	Cancer	Fasted	≤1.5 mg/dL	≤3.0× ULN	≤3.0× ULN	57 (31–73)	[11]
1,600	50,597 (27,364–93,450)b	39,207	−22.5	Cancer	Not fasted	≤2.0 mg/dL	≤3.0× ULN	≤3.0× ULN	55 (38–70)	[5]
1,600	87,941 (49,348–156,717)b	39,207	−55.4	Cancer	Fasted	≤1.5× ULN	≤2.5 × ULN	≤2.5× ULN	60 (37–73)	[13]
1,600	39,067b	39,207	0.4	Cancer	Fasted	≤2.0 mg/dL	≤3.0× ULN	≤3.0× ULN	66 (25–85)	[15]
1,800	47,671b	44,108	−7.5	Cancer	Fasted	≤2.0 mg/dL	≤3.0× ULN	≤3.0× ULN	67 (25–86)	[15]
1,800	67,895 (25,658–179,656)b	44,108	−35.0	Cancer	Fasted	≤1.5× ULN	≤2.5 × ULN	≤2.5× ULN	60 (37–73)	[13]

^aAUC_τ is the mean (90 % confidence interval) of the steady-state area under the concentration–time curve calculated within the dosing interval (0–24 h)

^bAUC_τ is the geometric mean (95 % confidence interval) of the steady-state area under the concentration–time curve calculated within the dosing interval (0–24 h)

^cPE% is the prediction error

^dBilirubin, aspartate transaminase (AST) and alanine transaminase (ALT) are measures of liver function. ULN is upper limit of normal

^eMedian age (range)