Table 3.

Summary of pharmacokinetic parameters

HCC, Child–Pugh AHCC, Child–Pugh BSolid tumor
12 mg (MTD)16 mg8 mg (MTD)12 mg12 mg25 mg (MTD)
ParameterUnit(n = 6)(n = 3)(n = 6)(n = 5)(n = 11)(n = 24)
Single doseAUC(0–24 h)ng*h/mL2020 (170)3280 (961)1250 (399)2140 (1030)1655 (555)4075 (1666)
Cmaxng/mL212 (70.8)344 (166)146 (56.9)254 (169)260 (108)631 (234)
tmaxh2.00 (0.97, 5.95)1.97 (0.97, 4.00)2.02 (0.50, 3.93)2.00 (1.00, 3.98)2.53 (0.98, 5.05)1.53 (0.98, 3.00)
t1/2h7.19 (0.77)a8.18 (2.36)9.10 (2.28)10.1 (4.1)6.0 (0.5)b,f5.9 (1.0)c
CL/FL/h5.30 (0.34)a4.33 (0.83)5.99 (2.25)5.76 (3.35)6.6 (1.3)f6.9 (3.4)c
Multiple doseAUC(0−τ)ng*h/mL3120 (566)a5110 (976)d1770 (340)3960 (1990)d2059 (792)e4236 (1127)g
Css, maxng/mL346 (75.4)a402 (62.9)d167 (40.4)349 (180)d291 (146)e545 (183)g
C24 hng/mL43.1 (21.7)a84.6 (33.1)d29.9 (13.4)64.0 (34.7)d22.3 (7.4)f45.1 (20.2)a
tss, maxh1.95 (1.00, 3.98)a3.92d (3.83, 4.00)2.03 (1.98, 4.02)2.00 (1.97, 2.02)d1.54 (0.97, 4.98)e2.84 (1.33, 4.92)g
t1/2, ssh8.76 (2.62)a8.98 (2.15)d10.2 (3.1)9.74 (0.933)d6.9 (1.2)e6.0 (0.7)g
CLss/FL/h3.95 (0.78)a3.19 (0.608)d4.69 (1.07)3.47 (1.75)d6.9 (3.4)e6.4 (2.3)g

NOTE: AUC(0–24 h), area under the concentration–time curve from zero time to 24 hours; AUC(0−τ), area under the concentration–time curve over the dosing interval on multiple dosing; Css, max, maximum observed concentration at steady state; CL/F, oral clearance; CLss/F, oral clearance at steady state; tmax, time at which drug concentration is the highest; tss, max, time at which the highest drug concentration occurs at steady state; t1/2, terminal elimination phase half-life; C24 h, plasma concentration at 24 hours after administration. The number of patients receiving multiple doses in each of the following groups: CP-A 12 mg, CP-A 16 mg, CP-B 8 mg, CP-B 12 mg, solid tumor 12 mg, and solid tumor 25 mg equals 5, 2, 6, 2, 8, and 4, respectively.

Data are represented as mean (SD), except for tmax and tss, max, which are represented as median (minimum − maximum).

  • an = 5; bn = 11; cn = 23; dn = 2; en = 8; fn = 10; gn = 4.