Pharmacokinetic models

1. Advanced
Biopharmaceutics and
Pharmacokinetics
Prepared and presented by,
Mr. Namdeo Shinde
M. Pharm. (Pharmaceutics)
Satara college of pharmacy, Satara.
PHARMACOKINETIC MODELS
In Silico, In-Vitro & In-Situ

2. Pharmacokinetic studies involves the processes of
absorption, distribution, metabolism and excretion.
Models:
1. In Silico Models
2. In Vitro Models
3. In Situ Models
4. Ex-Vivo Model
5. In-Vivo Model
Introduction
Mr. Namdeo Shinde, SCOP, Satara

3. 1. In Silico Models (In the Computer):
In Silico
Models
Mr. Namdeo Shinde, SCOP, Satara
In silico modelling, in which computer models are developed
to model a pharmacologic or physiologic process, is a logical
extension of controlled in vitro experimentation. It is the
natural result of the explosive increase in computing power
available to the research scientist at continually decreasing
cost.

4. 1. In Silico Models (In the Computer):
In silico Modeling is otherwise known as computer modeling.
Computation models using computer for the evaluation of
biological processes/responses based on the chemical structure
or physicochemical property of drugs.
Intestinal drug absorption is predicted based on the
chemical structure, on the lines of QSAR.
In Silico
Models
Mr. Namdeo Shinde, SCOP, Satara

5. Mr. Namdeo Shinde, SCOP, Satara

6. Sophisticated software's are utilized for this purpose.
QMPRPlus (Quantitative Molecular Permeability relationship)
&
GastroPlus are used for studying drug absorption.
This models are useful for predicting the desired
chemical structure before taking up for synthesis.
In Silico
Models
Mr. Namdeo Shinde, SCOP, Satara

7. 2. In Vitro Models (In the Glass):
 Biological effects are observed in Glassman Apparatus
(Test tube) / artificial environment.
 Transport of drug across biomembrane is mimicked in the
Glassman apparatus.
 Artificial membranes are used. (Cellulose acetate/polymer
membrane)
 Scope of this model is improved using isolated tissues
In Vitro
Models
Mr. Namdeo Shinde, SCOP, Satara

8. Mr. Namdeo Shinde, SCOP, Satara

9. 2. In Vitro Models (In the Glass):
 Models are utilized for studying drug absorptions.
 In drug metabolic studies, enzymes, receptors and drug
protein interactions are studied using chemical methods.
 Hepatic enzymes (Cyt. P450) are used for obtaining
information on enzymology and establishing SAR.
In Vitro
Models
Mr. Namdeo Shinde, SCOP, Satara

10. Mr. Namdeo Shinde, SCOP, Satara

11. Mr. Namdeo Shinde, SCOP, Satara

12. Advantages:
 Simple and quick to perform.
 Experimental conditions can be manipulated closer to
real life situations.
 In In-Vitro models, visibility of the tissue is
questionable and tike taken for preparation of
sample is long.
In Vitro
Models
Mr. Namdeo Shinde, SCOP, Satara

13. In-Situ Models (At the site):
In situ models are those used locally in the same place where
the phenomenon is taking place without isolating it from other
systems or altering the original conditions of the test.
In-Situ
Models
Mr. Namdeo Shinde, SCOP, Satara

14. In-Situ Models (At the site)
The pharmacological effects are studied at the site of
origin in the body, without invasion of neighboring
tissues.
 Drug absorption is studied using rat gut method. In
thid Rat is anaesthetized, intestine is exposed and
drug absorption is studied. Intestine is not
completely separated from body, tissue visibility is
maintained, lymphatic system and blood supply are
In-Situ
Models
Mr. Namdeo Shinde, SCOP, Satara

15. Advantages:
 It can be employed for comparative evaluation.
 Same preparation can be used for further
investigation after giving adequate washout period.
In-Situ
Models
Mr. Namdeo Shinde, SCOP, Satara

16. Ex-Vivo Models (Outside the body)
Models in which an organ may be repaired by surgery
and then returned to the original state.
 This methods are considered as outside the body.
 Ex-vivo perfusion model is used for study of
transport and fluid flow within the bone under
controlled mechanical loading conditions.
 Cell lines are used for studying properties it
Ex-Vivo
Models
Mr. Namdeo Shinde, SCOP, Satara

17. Ex-Vivo models permit the development of
specific cell line culture obtained from the patient
(Stem cells)
Ex-Vivo
Models
Mr. Namdeo Shinde, SCOP, Satara

18. Mr. Namdeo Shinde, SCOP, Satara

19. In-Vivo Models (In the body)
In-Vivo models in which biological responses are
studied within the living body.
 In this, entire animal is used for evaluation process.
 IntelSite capsules are used for studying the drug
absorption.
 Radiotracers are tagged to the drug and absorption
and metabolism studied.
In-Vivo
Models
Mr. Namdeo Shinde, SCOP, Satara

20. Mr. Namdeo Shinde, SCOP, Satara

21. Mr. Namdeo Shinde, SCOP, Satara

22. This models are required to examine additional
factors contributing absorption and metabolism.
Disadvantages:
 In-Vivo methods are laborious and time
consuming.
 Study requires development of sensitive and
specific analytical methods.
In-Vivo
Models
Mr. Namdeo Shinde, SCOP, Satara