Research Article

Identification and Preclinical Pharmacology of the -Secretase Modulator BMS-869780

Table 2

PK/PD model values from mouse and rat studies.

ParameterUnitsMouseCV (%)RatCV (%)

PK parameters
Kelh−10.2844.10.1048.4
L/kg1.9448.31.9443.8
Ka1 (10 mg/kg)h−10.1956.0
Ka1 (30 mg/kg)h−10.1129.8
Ka2 (100 mg/kg)h−10.04630.0

PD parameters
h−10.7224.90.4851.4
IC50
nM39799.16189226.4
%100Fixed100Fixed

1Fixed1Fixed

%/h72Calculated48Calculated

Kel-first order rate constant for drug elimination; -volume of distribution; Ka rate constant for drug absorption; -first order rate constant for degradation of A 1-42 or A 1-40; -plasma concentration required for 50% inhibition of Aβ1-42 or Aβ1-40 production; is the response in Aβ1-42 or Aβ1-40 levels, assumed 100% at time zero, ; -range of the response of Aβ1-42 or Aβ1-40 levels; -zero order constant for Aβ1-42 or Aβ1-40 production.