Table 2.

PK parameters of vorinostat following oral administration of single or multiple doses of 400 mg

DoseSingle doseSingle doseMultiple doses*GMRP
DietFastedFedFed
N232014
AUC0-∞, μmol/L h (range)3.87 (2.33-9.86)5.33 (3.41-9.34)1.38<0.001
AUC0-24 h, μmol/L h (range)3.82 (2.31-9.85)5.33 (3.51-9.24)6.46 (4.06-10.47)1.21§,0.019§; 0.010
Cmax, μmol/L (range)1.12 (0.56-1.76)1.02 (0.43-2.98)1.13 (0.46-2.64)0.910.451
Tmax, h (range)1.50 (0.5-1.52)4.00 (2.0-10.0)4.21 (0.5-14.0)<0.001; 0.869**
Apparent t1/2, h†† (range)1.74 (0.93-18.44)1.44 (0.79-3.77)1.34 (0.83-3.88)0.036
fe‡‡ (range)0.0021 (0.0001-0.0051)0.0030 (0.0008-0.0089)0.0037 (0.001-0.0092)
  • Abbreviation: GMR, geometric mean ratio.

  • * Once daily for 22 days.

  • Geometric mean.

  • Single dose fed/single dose fasted.

  • § Accumulation ratio: AUC0-24 h multiple dose fed/AUC0-24 h single dose fed.

  • Linearity ratio: AUC0-24 h multiple dose fed/AUC0-8 single dose fed.

  • Median.

  • ** Multiple dose fed/single dose fed.

  • †† Harmonic mean.

  • ‡‡ fe = fraction of dose excreted unchanged in urine; data are arithmetic mean (single dose fasted, n = 22; single dose fed, n = 21; multiple dose fed, n = 12).