Toxicokinetics studies.. (toxicokinetics evaluation in preclinical studies)
1. Toxicokinetics
Submitted to : Prof. Vaishnavi ma’am. Submitted by: jamdade sonali lala
Pharmacology department M pharm 1st pharmacology
Sudhakar Rao Naik Institute Of Pharmacy Pusad
2. Content
Introduction
Process are involved in toxicokinetics
General principle to be considered
Toxicokinetic studies in preclinical stages.
Toxicokinetic studies in clinical phases .
3. Introduction
toxicokinetics describe the rate of a chemical enter the body and how
the compound metabolise and excrete once it is in the Body.
Toxicokinetics deals with absorption, distribution biotransformation and
excretion of chemical.
Toxicokinetic defined by the ICH as the generation of pharmacokinetic data
,either as an integral component in conduct of non clinical toxicity studies
or in specially defined supportive studies , to assess systemic exposure.
While developing a molecule as a therapeutic agent researchers consider
not only benefit but also risk associated with it .
Hence toxicological evaluation got more important in drug development
stages especially in pre clinical stages.
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5. • Absorption
absorption Is the process by which the chemical enters the
body. It depends on the route of administration .
Oral route: the GIT Is most important rote of absorption, as
most acute poisonings involve ingestions.
Dermal rout: lipid solubility of a substance is an important
Factor affecting the degree of absorption through the skin.
Inhalational route: toxic fumes, particulate and noxious gases
may be absorbed through the lungs.
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14. General principles to be considered
1. Quantification of exposure.
2.setting of dose levels
low dose levels
Intermediate dose levels.
High dose levels
3.extent of exposure assessment in toxicity
studies.
4. complicating factors in exposure
interpretation
5. Route of administration.
7. statistical evaluation of data
8. Analytical methods
9. Reporting
15. Toxicokinetics studies in preclinical stage:
1.saftey assessment
2. Single dose and rising dose studies repeated Dose toxicity studies
3. repeated dose toxicity studies
4. Genotoxicity studies.
5. Reproduction toxicity studies.
Studies of fertility
In pregnant and lactating animal.
6. carcinogenicity studies.
Toxicokinetic studies in Clinical Phases:
approaches to decrease the animal usage in toxicokinetics
dried blood spot technology.
Alternative approaches to animal models.
Physiologically based pharmacokinetic modelling.
