TABLE 1

Duration of pharmacodynamic effect measured as decrease of bioluminescence over time

AUC and t1/2 were calculated over 25 days. Bioluminescence −log2-fold change represents bioluminescence reduction at day 3. An extra sum-of-squares F-test was performed. Bioluminescence was measured at day 3.

Dose of siRNABioluminescence ChangePD Effect t1/2Duration of the PD Effect AUC
−log2-fold (%)days (95% CI)relative bioluminescence × days
0.3 mg/kg0.8 (43)5.3 (2.7, 208)9.1
1 mg/kg2.4 (81)10.0 (8.6, 12.0)32.1
3 mg/kg3.8 (93)*8.6 (7.6, 9.9)47.3
6 mg/kg4.7 (96)10.7 (9.6, 12.1)66.0
  • AUC = area under the curve; CI = confidence interval; PD = pharmacodynamic; t1/2 = half-life

  • * F-test rejects 3 mg/kg being different from the others within the same experiment at the P > 0.01 significance level.