TABLE 1

Plasma pharmacokinetic parameters from subcutaneous dosing of multiple siRNAs to male (M) and female (F) rats and monkeys

siRNADosePlasma Pharmacokinetic Properties after Subcutaneous Administration to Monkeys
CmaxAUClastTmaxt1/2Dose at Cmax
MFMFMFMFMF
mg/kgng/mlh*ng/mlh%
10.340.657.6233266128.79ND0.1590.225
363459847003310222.782.110.2480.234
102530286015,70016,600221.965.840.2970.335
2189.317327946511NDND0.1050.203
58577024820426022NDND0.2010.165
102060203011,30010,600123.36ND0.2420.238
150.343.830.6189162112.382.840.1710.119
196.2112695686113.243.370.1130.131
335842521902680222.792.50.1400.166
3172.9641128722NDND0.08540.075
53862811930169022NDND0.09040.0658
252560213019,70012,000213.796.130.1200.0998
40.382.186.819820411NDND0.3210.339
124531184394910.52.551.520.2870.364
51140125056105850113.041.810.2680.293
206770448044,00038,000248.49ND0.3960.263
50.113.813.216822.541NDND0.1610.155
118112912,200114022ND9.940.2120.151
511609855590424022NDND0.2720.231
101570225012,10010,700223.58ND0.1840.263
60.342.237.61191270.526.22ND0.1650.147
190.699.758666244NDND0.1060.117
35492993140160042NDND0.2140.117
307760692063,10066,100242.7ND0.3030.270
siRNADosePlasma Pharmacokinetic Properties after Subcutaneous Administration to Rats
CmaxAUClastTmaxt1/2Dose at Cmax
MFMFMFMFMF
mg/kgng/mlh*ng/mlh%
10.334.729.139.616.811NDND0.4530.381
190.592.417417111NDND0.3550.363
329030149447911NDND0.3790.395
10143010603740212011ND1.380.5610.415
21981121411580.250.25ND2.540.3840.44
110211325416421NDND0.4010.442
5466386140011100.50.253.141.660.3650.303
55684551580124021NDND0.4450.357
109761170239029800.2523.31ND0.3830.458
101120155041503820226.33ND0.4410.607
32.52302853203710.50.5NDND0.360.447
551463993476210.5NDND0.4030.502
254450398010,3007080111.43ND0.6980.625
40.371.493.91011110.50.5NDND0.9331.23
13122074152620.50.50.969ND1.220.814
5943943184020200.250.50.9310.830.7390.741
204130499016,20010,6000.51ND1.020.8090.981
50.121.7221514.20.50.5ND0.9870.8490.865
12713353814980.50.51.03ND1.061.32
51010874182020200.511.051.110.7930.687
10220024304770462010.50.914ND0.8640.955
  • F, female; M, male; ND, not determined.