## Estimating An Dn and Do Values

To facilitate use of the model, estimates for the Absorption, Dissolution and Dose Numbers are necessary. Many of the variables used to calculate An, Dn, and Do are physiologically based and therefore do not change as new compounds are tested. In addition, the density of the solid and the molecular diffusivity (related to molecular weight) do not vary significantly across typical drug-like organic compounds, and so representative values can be used with reasonable accuracy. Therefore, a simple method for estimating An, Dn, and Do is to combine the relatively constant physiological and physical parameters into single factors which are then multiplied by the compound specific variables. Table 1 contains estimates for those factors for oral dosing into rat, dog, and human. The compound specific variables in the first column are multiplied by the species-specific factor to calculate the dimensionless variable in the last column. For example, solubility (in mg/ml) divided by the square of the estimated particle size (in |im) multiplied by 14850 yields the estimated dissolution number for humans.

The factors in Table 1 are approximations and are meant to be used a starting point. As one gathers data, it may become evident that a different value may be more appropriate. For example, a class of compounds may have regional permeability issues, and so the factor for permeability may have to be adjusted.

 Measured Property X (Estimated Factor) = Parameter Rat Dog Human Peff (cm/s) 54260 11781 9920 An Sol/r2 (mg/ml)/(^m2) 13500 7200 14850 Dn Dose/Sol (mg)/(mg/ml) 0.1 0.1 0.004 Do

Table 1. List of estimated multiplicative factors for converting measured physical properties of a drug into the dimensionless variables of absorption number, dissolution number, and dose number for rat, dog, and human.

Table 1. List of estimated multiplicative factors for converting measured physical properties of a drug into the dimensionless variables of absorption number, dissolution number, and dose number for rat, dog, and human.