Table 4.

Summary of pharmacokinetic parameters

CohortNo. of patientsNo. with pharmacokinetic dataMean (SD)Geometric mean peak-to-trough ratio (Cmax/Cmin)
Tmax, hCmax, nmol/LCmin*, nmol/LAUC0-τ, nmol/L × h
QD-10D (day 12)
    10 mg331.2 (0.3)923 (70)223 (76)9,023 (1,806)4.29
    20 mg661.5 (0.9)1779 (440)273 (134)14,134 (3,553)7.09
QID-14D (day 7, dose 2)
    25 mg771.2 (0.3)1,252 (669)887 (573)6,117 (3,533)1.55
    35 mg331.0 (0.5)1,169 (741)716 (464)5,479 (3,407)1.66
    45 mg661.4 (1.2)1,806 (604)1,208 (504)9,019 (3,250)1.55
    55 mg330.8 (0.8)2,173 (536)1,662 (222)10,820 (2,303)1.29
    60 mg330.3 (0.6)1,736 (185)1,217 (338)7,957 (1,397)1.46
    70 mg662.3 (1.9)3,498 (1,186)2,516 (881)17,037 (6,308)1.38
    80 mg662.1 (1.8)4,199 (2,804)3,010 (2,442)21,396 (15,498)1.58

NOTE: Cmin, minimum plasma concentration (trough value); AUC0-τ, area under the concentration time curve from time zero to τ, where τ = 24 in the QD cohorts and τ = 6 in the QID cohorts.

  • *Cmin was measured 24 hours after the daily dose on day 12 in the QD cohorts and 6 hours after the second dose on day 7 in the QID cohorts.

  • Administered 5 consecutive days/week for 2 weeks (i.e., days 1–5 and 8–12).