This document discusses computational modeling techniques used in drug disposition modeling. It describes two main modeling approaches: quantitative approaches like pharmacophore modeling and docking studies; and qualitative approaches like QSAR and QSPR studies. It then discusses how these techniques can be applied to model key aspects of drug disposition, including absorption, distribution, and excretion. The key aspects of drug absorption, distribution, and excretion are also summarized.

1. COMPUTATIONAL MODELING IN
DRUG DISPOSITION
Presented by :
Nikita Gidde.
M. Pharm, Sem-II.
Department of Pharmaceutics.
Rajarambapu College of pharmacy, Kasegaon.
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2. CONTENTS
1. Introduction
2. Modeling Technique
3. Drug Absorption
4. Drug Distribution
5. Drug Excretion
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3. INTRODUCTION
 Efficacy and selectivity against the biological target.
 Half of drug candidates fail at phase II and phase III clinical
trials because of the undesirable drug pharmacokinetics
properties
 To reduce the attrition rate at more expensive later stages, in
vitro evaluation of ADMET properties in the early phase of
drug discovery has widely adopted.
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4. MODELING TECHNIQUE
Consist 2 Approaches:
1.Quantitative approaches
Quantitative approaches represented by pharmacophore
modeling and flexible docking studies
Useful when there is an accumulation of knowledge against
certain target.
Three widely used automated pharmacophore perception tools
are DISCO (DIStance COmparisons), GASP (Genetic
Algorithm Similarity Program) and Catalyst
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5. MODELING TECHNIQUE CONT….
2.Qualitative approaches
The qualitative approaches represented by quantitative
structure-activity relationship (QSAR) and quantitative
structure-property relationship (QSPR) studies
It is essential to select the right mathematical tool for
most effective ADMET modeling.
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6. DRUG DISPOSITION
Drug
Disposition
Absorption
Solubility
Intestinal
Permeability
Active
Transport
Distribution
Volume of
Distribution
plasma-
protein
binding (PPB)
blood-brain
barrier (BBB)
permeability
Excretion
Renal
Hepatic
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7. DRUG ABSORPTION
 Because of its convenience and good patient compliance,
oral administration is the most preferred drug delivery
form.
 In general, drug bioavailability and absorption is the result
of the interplay between drug solubility and intestinal
permeability.
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8. DRUG DISTRIBUTION
 Distribution is an important aspect of drug’s
pharmacokinetic profile.
 The structural and physiochemical properties of a drug
determine the extent of distribution, which is mainly
reflected by three parameters:
1. volume of distribution (Vd),
2. plasma-protein binding (PPB) and
3. blood-brain barrier (BBB) permeability.
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9. DRUG EXCRETION
 The excretion or clearance of a drug is quantified by
plasma clearance, which is defined as plasma volume
that has been cleared completely free of drug per unit of
time.
 Together with Vd, it can assist in the calculation of drug
half-life, thus determining the dosage regimen.
 Hepatic and renal clearances are the two main
components of plasma clearance.
 Current modeling efforts are mainly focused on
estimating in vivo clearance from in vitro data.
 Just like other pharmacokinetic aspects, the hepatic and
renal clearance process is also complicated by
presence of active transporters.
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10. REFERENCES
 Ekins S, “Computer Applications in Pharmaceutical
Research and Development”, (2006) John Wiley
and Sons Inc., chapter 20, pp495-508
 Ekins S, Nikolsky Y and Nikolskaya T. Techniques:
Application of systems biology to absorption,
distribution, metabolism, excretion and toxicity.
Trends Pharmacol Sci 2005;26;202-9
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