TABLE 3

Summary of PK-PD model parameters estimated from cynomolgus monkey studies with GNE-629

ParameterEstimate (% S.E.)a
PK Parameter
 ka (h−1)0.812 (7.0)
 ke (h−1)0.352 (3.4)
 k12 (h−1)0.164 (8.2)
 k21 (h−1)0.0827 (28)
 k1-csf (h−1)1.24 × 10−5 (16)
 kcsf-1 (h−1)2.27 (16)
 Vcsf (l/kg)2.00 × 10−3 (fixed)
 V1 (l/kg)12.3 (fixed)
 fu0.39 (fixed)
 CL1-csf (l/h per kilogram)b1.52 × 10−4
 CLcsf-1 (l/h per kilogram)b4.53 × 10−3
 Ratio CLcsf-1/CL1-csfb29.7
PD Parameter for CSF PD Model
 kinAPP (%/h)55.7 (26)
 k (h−1)0.140 (6.8)
 kα (h−1)0.411 (34)
 IC50 (µM)0.00328 (13)
PD Parameter for Plasma PD Model
 kinplasma (%/h)17.7 (7.8)
 IC50(plasma) (µM)0.0654 (13)

  • ↵a Fitted parameters are expressed as the estimate followed by the % standard error in parentheses.

  • ↵b Parameters are calculated as follows: CL1-csf = V1 × k1-csf; CLcsf-1 = Vcsf × kcsf-1.