Experimental determination of a drug's oral bioavailability in humans is cost and time consuming; therefore, is usually performed on preclinical animals. It is believed that animal data are predictive of human data; however, there are some doubts regarding the reliability of this concept. The aim of this study is to clarify whether it is possible to predict a correlation between human and animal bioavailability data based on structural parameters.
Oral bioavailability data of drugs for humans and preclinical animals (rats and dogs) were collected from the literature. Structural descriptors [Abraham solvation parameters, topological polar surface area (TPSA), logarithm of partition coefficient (logP) and logarithm of distribution coefficient at pH = 6.8 (logD6.8)] were calculated by ACD/Labs software. Data were divided into two classes by percentage deviation (PD) of oral bioavailability between humans and preclinical animals (PD < 40%: class I and PD > 40%: class II). Classification-based models were used to predict the class of each drug using structural parameters.
The results of this study revealed that logD6.8 is the main parameter for evaluation of the correlation between oral bioavailability in humans and animals. Moreover, the developed models using logistic regression based on logP, TPSA and Abraham solvation parameters are able to predict the class of a drug with 75% accuracy.
The structural parameters and developed models in this study can be used to find compounds that have an acceptable correlation between oral bioavailabilities in animals, i.e., rats and dogs, and humans.
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This article is a part of the results of S.B's Pharm.D thesis (project number: 61772) registered at Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
No funding was received for the conduct of this study.
Conflict of interest
All the authors have no conflict of interest to declare.
The study was approved by ethics committees of Tabriz University of Medical Sciences (IR.TBZMED.VCR.REC.1398.259).
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Beheshti, S., Shayanfar, A. Prediction of the Oral Bioavailability Correlation Between Humans and Preclinical Animals. Eur J Drug Metab Pharmacokinet (2020). https://doi.org/10.1007/s13318-020-00636-2