The maximum absorbable dose (MAD) provides a good conceptual tool to help anticipate oral absorption problems in the evaluation of drug candidates. It is calculated as follows:
where ka is the absorption rate constant in units of time-1 (i.e., min-1 or h-1), S is the solubility of the drug in relevant media in units of concentration (i.e., mg/mL), Vintestine is the volume of water in the small intestine in units of volume (i.e., mL), T is the small intestine transit time in units of time (i.e., min or h - this must be the same base units of time used for ka).
If the dose is greater than the MAD, incomplete absorption may occur. The MAD serves as a conceptual tool and can be useful for the RANK ORDERING of compounds during the drug candidate selection process. The ability of the MAD calculation to predict the actual MAD is difficult due to challenges in determination of the relevant solubility and intestinal absorption rate constant used in the MAD calculation. Small intestine transit times required for calculation of MAD is listed for rat, dog, and human in the next section.
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