Table 9.

Multiple dose lapatinib (25–1,200 mg) observed and predicted human half-life (t_1/2), maximum concentration (C_max) and time of maximum concentration (T_max)

Dose (mg)	Observed t1/2 (h)	Predicted t1/2 (h)	t1/2 PE%c	Observed Cmaxd (nM)	Predicted Cmax (nM)	Cmax PE%c	Observed Tmax (h)	Predicted Tmax (h)	Tmax PE%c	Reference
25	7.9a (6.4–9.8)	10.2	29.1	55 (38–81)	42	−23.7	2.7 (2.5–4.0)e	3.5	29.6	[4]
100	8.9a (6.1–12.9)	10.2	14.6	251 (150–420)	166	−33.9	3.0 (2.0–6.0)e	3.5	16.7	[4]
175	11.1a (7.3–16.8)	10.2	−8.1	429 (270–678)	290	−32.3	4.0 (3.0–6.0)e	3.5	−12.5	[4]
175	ND	10.2	NA	637	290	−54.5	ND	3.5	NA	[15]
375	ND	10.2	NA	706	622	−11.8	ND	3.5	NA	[15]
500	ND	10.2	NA	1,755 (1,308–2,375)	830	−52.7	ND	3.5	NA	[5]
650	ND	10.2	NA	2,237 (1,687–2,960)	1,078	−51.8	ND	3.5	NA	[5]
675	ND	10.2	NA	1,824	1,120	−38.6	ND	3.5	NA	[15]
900	ND	10.2	NA	1,807	1,493	−17.4	ND	3.5	NA	[15]
900	ND	10.2	NA	2,926 (2,082–4,130)	1,493	−49.0	ND	3.5	NA	[5]
900	23.1b (9.8–38.2)	10.2	−55.8	3,261 (2,270–4,683)	1,493	−54.2	4.0 (3.0–6.0)f	3.5	–12.5	[13]
1,000	ND	10.2	NA	3,184 (2,409–4,216)	1,659	−47.9	ND	3.5	NA	[5]
1,000	ND	10.2	NA	2,754 (2,203–3,442)	1,659	–39.8	ND	3.5	NA	[9]
1,200	ND	10.2	NA	2,100 (1,549–2,840)	1,990	−5.2	ND	3.5	NA	[5]
1,200	16.9b (15.1–34.3)	10.2	−39.6	2,952 (1,661–5,246)	1,990	−32.6	3.6 (3.0–7.9)f	3.5	−2.8	[13]
1,200	ND	10.2	NA	2,392	1,990	−16.8	ND	3.5	NA	[15]

ND not determined, NA not applicable

^at_1/2 is the terminal half-life geometric mean (95 % confidence interval)

^bt_1/2 is the terminal half-life median (95 % confidence interval)

^cPE% is the prediction error

^dIs the geometric mean (95 % confidence interval) of C_max

^eIs the median (range) of T_max

^fIs the median (95 % confidence interval) of T_max