Title:The Rule of Unity for Human Intestinal Absorption 2: Application to Pharmaceutical Drugs that are Marketed as Salts
VOLUME: 12 ISSUE: 2
Author(s):Raj B. Patel, Brittany Admire and Samuel H. Yalkowsky
Affiliation:Department of Pharmaceutical Sciences, College of Pharmacy, 1703 E. Mabel, Tucson, AZ 85721, USA.
Keywords:Absorption, oral dose, prediction, permeability, salts, solubility.
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.
