presentation.pptx

TOXICOKINETICS & SATURATION KINETICS
Objective
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

1. Noida Institute of Engineering and Technology (Pharmacy Institute) Greater Noida AN AUTONOMUS INSTITUTE TOXICOKINETICS & SATURATION KINETICS Presented by:- Shilajit Das(2 nd 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. Rodents(rat and mice ) Non-rodents(dogs) 2

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. 3

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. 4

5. Toxicokinetic study goals A. Pretoxicology study Recommend selection of species Route selection Develop data for dose se lection B. Toxicology study Provide estimate of internal dose Determine effects of age and multiple Exposure on kinetics

6. General principles of TK studies Quantification of exposure Justification of time points for sampling Dose level toxicity testing Ratifying factor Route of administration Determination of metabolites Statistical evaluation of data Analytical methods Reporting 6

7. Protocol for toxicokinetic validation 7 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 8

9. Drugs monitored for its toxicity 9

10. Saturation Kinetics 10 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 12 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