The document provides an overview of pharmacokinetic modeling, specifically one-compartment models used for predicting the absorption, distribution, metabolism, and excretion of substances. It discusses various principles such as first-order and zero-order kinetics, as well as specific modeling techniques like compartmental and physiologic models. Additionally, it includes references to literature and online resources relevant to pharmacokinetics and biopharmaceutics.

1. ANUPAM SAHA
SUNIRMAL BHATTACHARJEE
Email ID - sunirmal.pharma@gmail.com
PHARMACOKINETIC- ONE
COMPARTMENT MODELING

2. INTRODUCTION:
• Pharmacokinetics
• Clinical pharmacokinetics
• Compartments

3. BASIC PRINCIPLE OF PHARMACOKINETICS

4. One Compartment Open Model
• Physiologically based pharmacokinetic (PBPK)modeling is a
mathematical modeling technique for predicting the absorption,
distribution, metabolism and excretion (ADME) of synthetic or natural
chemical substances in humans and other animal species. This is
called pharmacokinetic model.
• Pharmacokinetic models are developed based on certain
assumptions. It should be remembered that application of mathematic
to physiological events means to correlate mathematics with
physiological events , so assumption made should be realistic and
practical.

5. The following assumptions
are : -
– The process of drug absorption from the absorption site may be
explained by the first order kinetics.
– Once a drug enters the systemic circulation, it rapidly distributes to other
body fluids and tissue , and a dynamic equilibrium is achieved
instantaneously between the drug in the blood and the drug in other
tissues.
– Any changes that occur in the plasma levels of a drug reflects
proportional changes in the tissue drug level.
– Elimination in the drug from body follows an apparent first order rate
constant.

6. • ZERO ORDER KINETICS
Zero order Half- Life
t1/2 = C0 /2K0
• FIRST- ORDER KINETICS
First-Order Half-Life
• Mixed-Order Kinetics
t1/2 = o.693/K
dC/dt = K0C0 =-K0

7. PHARMACOKINETIC MODELS
• Compartment model
Mammiliary model
Caternary model
• Noncompartmental model
• Physiologic model

8. COMPARTMENT MODELING
ONE COMPARTMENT OPEN MODEL
•Intravenous bolus administration
•Intravenous infusion
• Extravascular administration
A) Extravascular administration zero order
B) Extravascular administration first order
• Disposition as viewed from urine

9. INTRAVENOUS BOLUS ADMINISTRATION
dX/dt = Rate in (availability) – Rate out (elimination)
dX/dt = - KE X

10. • Elimination Rate Constant
KE= Km + Ke
Pharmacokinetic parameters
dX/dt = - KE X
Integration
lnX = lnX0 – KE t
X = X0 e-Ket
logX = logX0 – KEt / 2.303 logC = logC0 – KEt / 2.303

11. • Elimination Half-Life
• Apparent Volume of Distribution

12. • AUC Estimation
X0 = Ke Vd AUC
• Clearance
• Total Body Clearance
ClT = ClR + ClNR
𝑉𝑑 =
𝑋0
𝐾𝑒 (𝐴𝑈𝐶)

13. One Compartment Open Model – Intravenous
continuous infusion
= R0 - KEX
Integration

14. Loading Dose Plus IV Infusion
XO,L = CSSVd
XO,L =

15. Extravascular Administration
>
=
<

16. Urinary Excretion Data
• Useful when there is a lack of sensitive analytical
technique
• It is more convenient
• Less sensitive analytical method required
• Direct measurement of bioavailability
• CLR =

17. References
• Ali j.et al (2004) “Biopharmaceutics and Pharmacokinetics” 2nd ed. Birla Publications Pvt. Ltd.
Delhi, 64-115
• Analysis of blood & urine data, Compartment models, kinetics of one & two compartment
models [Online] Available at <http://pharmaquest. weebly.com /uploads/9/9/4 /2/994
2916/blood_urine_data.pdf> [Accessed 15-8-2012]
• Brahmankar D.M., Jaiswal S.B. (2009) “Biopharmaceutics and Pharmacokinetics A Treatise”
2nd ed. Vallabh Prakashan, Delhi p.p. 235-298
• Cheng HY, Jusko WJ (1998) Mean residence time concepts for pharmacokinetic systems
with nonlinear drug elimination described by the Michaelis-Menten equation [Online]
Available at <http://www.ncbi.nlm.nih.gov/pubmed/3244627> [Accessed 05-8-2012]
• Compartmental Analysis [Online] available at <http://www.uq.edu.au/ pharmacy/sduf
full/Comp _ analysis.pdf> [Accessed 1-8-2012]
• Dhillon S. and Gill K. Basic pharmacokinetics [Online] Available at <http:// www.
pharmpress.com/files/docs/clinical_pharmacokinetics_samplechapter.pdf>[Accessed 12-8 –
2012]
• Introduction to Pharmacokinetics and Pharmacodynamics [Online] Available at <http://w
ww.ashp.org/DocLibrary/Bookstore/P2418-Chapter1.aspx> [Accessed 12-8-2012]
• Mathematics in Pharmacokinetics What and Why (A second attempt to make it clearer)
[Online] Available at<http://www.cop.ufl.edu/wp-content/uploads/2010/10/PKMATH
stark.pdf> [Accessed 24-8-2012]

18. • Mathematics in Pharmacokinetics What and Why (A second attempt to make it
clearer) [Online] Available at<http://www.cop.ufl.edu/wp-content/uploads/ 2010
/10/PKMATHstark.pdf> [Accessed 24-8-2012]
• Multi-compartment model [Online] Available at <http://en.wikipedia.org/wiki/Multi-com
partment_model> [Accessed 29-8-2012]
• Pharmacokinetic Modeling [Online] Available at <http://www.nap.e du/openboo
k.php? record_ I d=11707&page=29> [Accessed 15-7-2012]
• Pharmacokinetics and Biopharmaceutics (46:138) Lecture tutorial [Online] Available
at <http://www.uiowa.edu/~c046138/tut-noncomp.htm> [Accessed 17-7-2012]
• Shargel L. et al (2004) “Applied Biopharmaceutics and Pharmacokinetics” 5th ed. Mc
• Graw Hill’s, North Carolina
• Tipnis H.P. Nagarsenker M.S. (2003) “Introduction to Biopharmaceutics and
Pharmacokinetics” 2nd ed. 2003 Nirali Prakashan India 61-92
• Venkateswarlu V. (2004) “Biopharmaceutics and Pharmacokinetics” Pharma Book
Syndicate, Hyderabad 170
• What are compartmental models? [Online] Available at<http://blog.learnpkpd. com/
2011/01/05/what-are-compartmental-models/> [Accessed 29-8-2012]
• Available <http://www.sciencedirect.com/science/article/pii/S 0304401705002591&d
o cid=v8E_yvAgSz46FM&imgurl=http://ars.els-cdn.com/content/image/>[Accessed
9-8-2012]