Table 4.

Pharmacokinetic results from repeated-dose analysis

Mean (SD) (CV%)
Dose, mgt1/2z, hTmax, hCmax, ng/mlCmax/D, ng/ml/mgTlast, hAUC0–24, h ng/mlAUC0–24/D, h ng/ml/mgCl/F, ml/hAR CmaxAR AUCAUClast, h ng/ml
21/7n = 1n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3
3069.8 (NC) (NC)2.69 (1.13) (42.0)12,300 (5,510) (44.7)411 (184) (44.7)143 (82.7) (57.7)2,58,000 (1,12,000) (43.6)8,589 (3,743) (44.0)140 (82) (58.0)10.34 (7.98) (77.2)11.91 (8.31) (69.8)9,44,000 (6,63,000) (70.3)
n = 0n = 2n = 2n = 2n = 2n = 2n = 2n = 2n = 2n = 2n = 2
60NC4.04 (0.0589) (1.46)10,200 (5,140) (50.6)169 (85.7) (50.6)192 (1.77) (0.92)2,29,000 (1,22,000) (53.3)3,808 (2,039) (54.0)307 (164) (54.0)4.76 (1.04) (21.8)5.01 (0.46) (9.2)13,40,000 (5,84,000) (43.5)
n = 1n = 2n = 2n = 2n = 2n = 2n = 2n = 2n = 2n = 2n = 2
120103 (NC) (NC)14.0 (14.2) (101)44,000 (919) (2.1)366 (7.66) (2.1)179 (14.5) (8.1)9,82,000 (50,200) (5.1)8,192 (436) (5.3)122 (7) (5.3)6.02 (0.14) (2.4)6.42 (0.28) (4.4)50,10,000 (88,400) (1.8)
n = 1n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3
22579.8 (NC) (NC)6.69 (2.29) (34.2)45,700 (39,800) (87)203 (177) (87)137 (77.8) (56.8)10,60,000 (9,39,000) (89.0)4,699 (4,185) (89.0)334 (213) (64.0)5.25 (2.26) (43.0)6.49 (3.00) (46.2)51,80,000 (61,10,000) (118.0)
n = 1n = 4n = 4n = 4n = 4n = 3n = 3n = 3n = 4n = 3n = 4
40079.5 (NC) (NC)3.63 (3.25) (89.7)99,700 (36,600) (36.7)249 (91.4) (36.7)109 (97.8) (89.5)22,60,000 (2,35,000) (10.4)5,642 (586) (10)178 (18) (10)10.98 (6.62) (60.3)10.64 (5.80) (54.5)78,40,000 (69,90,000) (89.2)
n = 2n = 9n = 9n = 9n = 9n = 9n = 9n = 9n = 9n = 9n = 9
60088.0 (21.3) (24.2)4.22 (7.54) (179)95,200 (43,600) (45.8)159 (72.7) (45.8)156 (62.3) (39.9)20,60,000 (9,38,000) (45.6)3,429 (1,562) (46.0)462 (484) (105.0)8.05 (6.49) (80.6)8.98 (7.07) (78.7)1,02,00,000 (59,40,000) (58.4)
NCn = 1n = 1n = 1n = 1n = 1n = 1n = 1n = 1n = 1n = 1
900NC0.5.9 (NC) (NA)1,36,000 (NC) (NC)151 (NC) (NC)217 (NC) (NC)29,40,000 (NC) (NC)3,267 (NC) (NC)306 (NC) (NC)12 (NC) (NC)13.0 (NC) (NC)2,04,00,000 (NC) (NC)
CDDn = 0n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3
100NC6.67 (2.31) (NC)23,800 (11,500) (34.6)238 (115) (48.2)23.9 (0.173) (0.7)54,1000 (2,76,132) (51)5,410 (2,761) (51.0)219 (103) (47.0)5.15 (1.38) (26.9)5.88 (1.62) (27.5)5,41,000 (2,76,000) (51.0)
n = 0n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3n = 3
400NC4.00 (3.46) (86.6)1,18,000 (51,900) (44.1)294 (130) (44.1)24.4 (1.65) (6.8)26,53,333 (11,66,462) (44.0)6,633 (2,916) (44.0)182 (107) (59.0)10.79 (6.88) (63.7)11.95 (7.74) (64.8)26,50,000 (11,60,000) (43.9)
n = 0n = 14n = 14n = 14n = 14n = 14n = 14n = 14n = 14n = 14n = 14
600NC3.36 (3.03) (90.2)87,200 (40,300) (46.3)145 (67.2) (46.3)24.4 (1.1) (4.51)19,31,286 (91,3057) (47.3)3,219 (1,522) (47.3)439 (329) (75.0)10.5 (4.3) (40.7)13.0 (6.8) (52.4)19,30,000 (9,13,000) (47.3)

Abbreviations: 21/7, 21 consecutive days on treatment followed by 7 days off treatment; AUClast, area under the concentration–time curve up to the last measurable concentration; AUC0–24, area under the concentration–time curve up to 24 hours; AR, accumulation ratio; Cmax, maximum concentration; CDD, continuous once-daily dosing; CL, apparent clearance; CV, coefficient of variation; D, dose normalized; NC, not calculated; tlast, time to last measurable concentration; tmax, time to maximum concentration; t1/2, z, terminal elimination half-life.