Table 2

Pharmacokineticsa

ParameterDose (mg/kg/day)
0.51.01.52.03.0
No. of patients33366
C24-h,b μg/ml0.11 ± .020.28 ± .080.44 ± .060.49 ± .071.07 ± .40
C7-day, μg/ml0.49 ± .310.19 ± .080.51 ± .300.33 ± .230.99 ± .83
C14-day, μg/ml0.28 ± .240.23 ± .070.45 ± .110.68 ± .161.86 ± .60
CEOI, μg/ml0.08c0.25 ± .060.38 ± .160.53 ± .240.89 ± .30
CSS, μg/ml0.18 ± .090.24 ± .020.41 ± .130.50 ± .131.26 ± .15
AUCSS, μg*min/ml253 ± 123349 ± 22.5596 ± 192723 ± 1811821 ± 215
Cl, ml/min/kg2.30 ± 1.042.87 ± .182.67 ± .732.88 ± .651.66 ± .21
Vinf, ml/kgnc186 ± 1296 ± 26254 ± 57146 ± 19
t1/2, minnc45 ± 1825 ± 1361 ± 1461 ± 5.4
% intact 24 hnc75.6 ± 4.865 ± 13.154 ± 8.152.4 ± 10.5
% intact EOInc66.1 ± 3.650.7 ± 7.252.9 ± 10.945 ± 3.7
  • a Values expressed as mean ± SD.

  • b C, concentration in plasma; EOI, end of infusion; ss, steady state; AUC, area under the curve; Vinf, apparent volume of infusion; nc, not calculated due to lack of measurable plasma concentrations postinfusion; % intact, % of intact antisense oligonucleotide.

  • c n = 2.