How does Cloe® PK choose the range of values for each property during sensitivity analysis?
A. Results are provided for which your values of the input properties have been varied through pre-determined ranges. The ranges have been chosen to represent relatively small changes – generally 3-fold – in properties of your compound. Thus: • Intrinsic clearance, solubility and Caco-2 permeability are varied through 3-fold ranges below and above your initial input value. • LogP octanol/water is varied through ±0.5, which corresponds to a 3-fold variation above and below the value of P, the partition coefficient. • The range in fraction unbound in plasma corresponds to a 3-fold variation in the plasma protein binding constant. The sole exception to this is if your initial value is exactly 1. In this case, fraction unbound in plasma is varied between 0.5 and 1. • Blood:plasma ratio is varied such that the difference between its value and the value of (1- haematocrit) is varied through a 3-fold range. The ranges have been deliberately set to be relatively small because, as potential cha
