This document summarizes information about toxicokinetics and saturation kinetics studies presented by Shilajit Das. It discusses how toxicokinetics studies are used to evaluate systemic drug exposure in animals and relate it to dose levels and toxicity findings to assess human safety. It provides the objectives, goals and general principles of toxicokinetics studies including quantifying exposure, justifying sampling timepoints, and determining metabolites. It also discusses how saturation kinetics can cause non-linear pharmacokinetics when enzyme or carrier capacities are exceeded, and how this non-linearity can be detected by evaluating parameters like bioavailability and clearance at different doses.

1. Noida Institute of Engineering and Technology (Pharmacy Institute)
Greater Noida
AN AUTONOMUS INSTITUTE
TOXICOKINETICS & SATURATION KINETICS
Presented by:-
Shilajit Das(2nd Sem)
M . Pharm (Pharmacology)
Submitted to:-
Dr . Saumya Das
Associate Professor
NIET(Pharmacy Institute)
Greater Noida

2. Introduction
• Toxicokinetics is defined as the generation of
pharmacokinetics data to design, conduct &
Interpretation of drug safety evaluation studies.
• In these studies, a minimum of two animal species
are employed, as per regulation of FDA.
1. Rodents(rat and mice )
2. Non-rodents(dogs)
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3. Need of toxicokinetic Studies
• Generation of kinetic data for systemic exposure and
toxicity assessment of the drug.
• Safety/risk ratio
• Important in drug development stages especially in
preclinical stage.
• Useful for the setting safe dose level in clinical phases.
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4. Objectives
To describe the systemic exposure achieved in
animals and its relationship to dose level and time
course of the toxicity study.
To relate the exposure achieved in toxicity studies to
toxicological findings and contribute to assessment of
human safety clinically.
To provide information which, in conjunction with the
toxicity findings contributes to the design of
subsequent non- clinical toxicity studies.
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5. Toxicokinetic study goals
A. Pretoxicology study
• Recommend selection of species
• Route selection
• Develop data for dose selection
B. Toxicology study
• Provide estimate of internal dose
• Determine effects of age and
multiple
• Exposure on kinetics

6. General principles of TK studies
A. Quantification of exposure
B. Justification of time points for sampling
C. Dose level toxicity testing
D. Ratifying factor
E. Route of administration
F. Determination of metabolites
G. Statistical evaluation of data
H. Analytical methods
I. Reporting
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7. Protocol for toxicokinetic validation
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Rational
Selection of animal
Preliminary study
Chronic study
Main study
Methods of Evaluation
Statistical Analysis
Results of Reporting

8. Applications of toxicokinetic studies
 TK evaluation is useful in selection of
 Dose
 Dosing of form
 alternative dosing route
 evaluation of toxicological mechanism
 use for the setting safe dose level in clinical phase
 TK studies also used to reduces the animal number.
 TK evaluation is very important in drug development phase in both regulatory
and scientific perspective
 TK data are practically used for the purpose of drug discovery such as lead
optimization and candidate- selection
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9. Drugs monitored for its toxicity
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10. Saturation Kinetics
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 Also known as nonlinear pharmacokinetics.
 The rate of process of a drug’s ADME are
dependent upon carrier or enzymes that are
substrate- specific.
 Have definite capacities and susceptible to
saturation high drug concentration.
 In such cases an essentially first- order kinetics
transform into a mixture of first- order and zero-
order rate processes and PK parameters change
with size of the administered dose.

11. Detection of non-linearity In pharmacokinetics
Determine of steady state plasma concentration at different
doses
Determine of some important PK parameters such as
Fraction bioavailability
Elimination half life or total systemic clearance

12. Reference
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• Barton, H.A.., et al.(2006) . Application of saturation , Metabolism and
Excretion(ADME)data in Agriculture chemical . Critical Revies in
Toxicology.36:9-35
• OECD Guideline for testing of chemical:- 428 “Skin Absorption : in vitro
method ”(Adopted 13 April 2004)
• Gingrich, J., Pu Y., Ehrhardt, R ., Karthik raj , R., Kannan
• Brahmankar ,D.M. and Jaiswal , S. B.(2009) Biopharmaceutics and
Pharmacokinetics, Delhi

13. THANK YOU