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Chapter 14
Quantitative Structure-Property Relationship
Analysis of Drugs’ Pharmacokinetics Within
the Framework of Biopharmaceutics
Classification System Using Simplex
Representation of Molecular Structure
N. Ya. Golovenko, I. Yu. Borisyuk, М. А. Kulinskiy, P. G. Polishchuk,
E. N. Мuratov and V. Е. Kuz’min
© Springer Science+Business Media Dordrecht 2014
L. Gorb et al. (eds.), Application of Computational Techniques in Pharmacy and Medicine,
Challenges and Advances in Computational Chemistry and Physics 17,
DOI 10.1007/978-94-017-9257-8_14
N. Ya. Golovenko () · I. Yu. Borisyuk · М. A. Kulinskiy · P. G. Polishchuk ·
E. N. Мuratov · V. E. Kuz’min
A.V. Bogatsky Physico-Chemical Institute NAS of Ukraine,
86 Lustdorfskaya Doroga, Odessa 65080, Ukraine
e-mail: n.golovenko@gmail.com
Abstract The Biopharmaceutics Classification System (BCS) categorizes drugs
into one of four biopharmaceutical classes according to their water solubility and
membrane permeability characteristics and broadly allows the prediction of the
rate-limiting step in the intestinal absorption process following oral administration.
When combined with the in vitro dissolution characteristics of the drug product, the
BCS takes into account three major factors: solubility, intestinal permeability, and
dissolution rate, all of which govern the rate and extent of oral drug absorption from
immediate-release (IR) solid oral-dosage forms. The concept of BCS provides a
better understanding of the relationship between drug release from the product and
the absorption process. This report reviews the current status of computational tools
in predicting the base properties (aqueous solubility, and passive absorption) of the
BCS and explores the application of the Simplex representation of molecular structure (SiRMS) QSAR approach in absorption (bioavailability) research. The main
advantages of SiRMS are consideration of the different physico–chemical properties of atoms, high robustness, predictivity, and interpretability of developed models
that creates good opportunities for molecular design. The reliability of developed
QSAR models as predictive virtual screening tools and their utility for targeted
drug design were validated by subsequent synthetic and biological experiments.
The SiRMS approach was implemented as “HiT QSAR” software. In addition, we
provide our perspective on the progress of research into an in silico equivalent to
the BCS.
Chapter 14
Quantitative Structure-Property Relationship
Analysis of Drugs’ Pharmacokinetics Within
the Framework of Biopharmaceutics
Classification System Using Simplex
Representation of Molecular Structure
N. Ya. Golovenko, I. Yu. Borisyuk, М. А. Kulinskiy, P. G. Polishchuk,
E. N. Мuratov and V. Е. Kuz’min
© Springer Science+Business Media Dordrecht 2014
L. Gorb et al. (eds.), Application of Computational Techniques in Pharmacy and Medicine,
Challenges and Advances in Computational Chemistry and Physics 17,
DOI 10.1007/978-94-017-9257-8_14
N. Ya. Golovenko () · I. Yu. Borisyuk · М. A. Kulinskiy · P. G. Polishchuk ·
E. N. Мuratov · V. E. Kuz’min
A.V. Bogatsky Physico-Chemical Institute NAS of Ukraine,
86 Lustdorfskaya Doroga, Odessa 65080, Ukraine
e-mail: n.golovenko@gmail.com
Abstract The Biopharmaceutics Classification System (BCS) categorizes drugs
into one of four biopharmaceutical classes according to their water solubility and
membrane permeability characteristics and broadly allows the prediction of the
rate-limiting step in the intestinal absorption process following oral administration.
When combined with the in vitro dissolution characteristics of the drug product, the
BCS takes into account three major factors: solubility, intestinal permeability, and
dissolution rate, all of which govern the rate and extent of oral drug absorption from
immediate-release (IR) solid oral-dosage forms. The concept of BCS provides a
better understanding of the relationship between drug release from the product and
the absorption process. This report reviews the current status of computational tools
in predicting the base properties (aqueous solubility, and passive absorption) of the
BCS and explores the application of the Simplex representation of molecular structure (SiRMS) QSAR approach in absorption (bioavailability) research. The main
advantages of SiRMS are consideration of the different physico–chemical properties of atoms, high robustness, predictivity, and interpretability of developed models
that creates good opportunities for molecular design. The reliability of developed
QSAR models as predictive virtual screening tools and their utility for targeted
drug design were validated by subsequent synthetic and biological experiments.
The SiRMS approach was implemented as “HiT QSAR” software. In addition, we
provide our perspective on the progress of research into an in silico equivalent to
the BCS.