Absorption

The absorption process is described by the ratio of the absorption rate to the GI transit rate. The calculated variable is termed the absorption number An and is given by:

A PeffJtRL

where

Peff is the effective permeability coefficient in the species of interest (cm/s)

R is the radius of the intestine (cm)

L is the intestinal length (cm)

Q is the volume flow rate down the GI tract (cm3/min)

In a relative sense, as the absorption rate becomes slower than the transit rate (An < 1), material passes through the intestine before it can be absorbed.

The variables R, L, and Q are assigned values based on species physiology and estimated intestinal transit time. The more sophisticated biopharmaceutic models account for regional permeability differences, but again, for the sake of simplicity, we assume permeability, Peff, is constant. As a first approximation, one assumes that absorption takes place in the small intestine only. If colonic absorption occurs, the effect is one of increasing An by a factor proportional to the relative increase in transit time.

Effective permeability is the variable into which a compound's behavior gets incorporated. An estimate for Peff can be determined by linking a permeability measurement in a cell-based (e.g., Caco2) or an artificial membrane (e.g., PAMPA) assay to a species-specific value through the means of standards. Metoprolol (Peff in human = 1.34e-6 cm/s) is often used as one of the standards since its permeability is the boundary for highly permeable compounds in the biopharma-ceutics classification scheme (BCS). (FDA, 2000)

Permeability may be reported as an absorption rate constant 'k' (min-1) as opposed to a Peff value. The conversion between the two is merely geometric surface to volume ratio of the intestine:

where

R is the intestinal radius of the species of interest

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