The Rule of Unity for Human Intestinal Absorption 2: Application to Pharmaceutical Drugs that are Marketed as Salts

Abstract

The efficiency of the human intestinal absorption (HIA) of the 59 drugs which are marketed as salts is predicted using the rule of unity. Intrinsic aqueous solubilities and partition coefficients along with the drug dose are used to calculate modified absorption potential (MAP) values. These values are shown to be related to the fraction of the dose that is absorbed upon oral administration in humans (FA). It is shown that the MAP value can distinguish between drugs that are poorly absorbed (FA <0.5) and those that are well absorbed (FA ≥ 0.5). Inspection of the data as well as a receiver operative characteristic (ROC) plot shows that a single critical MAP value can be used for predicting efficient human absorption of drugs. This forms the basis of a simple rule of unity based solely on in vitro data for predicting whether or not a drug will be well absorbed at a given dose.

A rule of unity for human intestinal absorption 3: Application to pharmaceuticals

“…Previously published rule of unity models by Sanghvi et al (2003) and Yalkowsky, Johnson, Sanghvi, and Machatha (2006) only apply to nonelectrolyte drugs which were reported to be passively absorbed after oral administration. While the rule of unity model by Patel, Admire, and Yalkowsky (2015) applies to the drugs that are marketed as salts with overall 91.5% correct prediction. To make the model more robust and generalized, all kinds of pharmaceuticals including salts, nonelectrolytes or drugs that are reported to be actively influxed or effluxed are incorporated in this work.…”