This document discusses toxicokinetics, which is the study of what the body does to chemicals, drugs, and other substances at toxic exposure levels. It covers the processes of absorption, distribution, biotransformation, and excretion that substances undergo in the body. Key toxicokinetic parameters discussed include area under the concentration curve, volume of distribution, clearance, and half-life - which provide information on how well and how quickly a substance is absorbed, distributed, metabolized, and eliminated from the body. Factors like age, health status, and the properties of the substance itself can impact these toxicokinetic processes and parameters.

1. TOXICOKINETICS
PHARM.D ( IV/VI)
SUB : CLINICAL TOXICOLOGY

2. TOXICOKINETICS
• It is a branch of science deals with toxicology
Including environmental and occupational
drugs and chemicals .
or
Study of kinetics for all substances at toxic
exposure levels .

3. INTRODUCTION :
• How a substance get into body and what
happens to it a body .
• The TK deals with what a body does with drug
when given relatively high does relative to
therapeutic dose .

4. PROCESS:
• ABSORPTION : ENTER INTO BODY
• DISTRIBUTION: MMOVES FROM SITE OF
ENTER INTO OTHRER BODY AREAS .
• BIOTRANSFORMATION :drug /substance
transforms into metabolite.
• EXCRETION :substance leaves the body.

5. FACTORS AFFECTING THE TOXICITY
SEVERITY
• DISPOSITION OF TOXICANT + BIOLOGICAL
REACTIVITY
• RESULTS IN
• XENOBIOTICS ENTERS INTO BODY

6. MOST IMPORTANT ASPECTS OF
DISPOSTION:
• ABSORPTION:
1. Duration and conc of substance at portal
entry.
2. Rate of amount absorbed .
• DISTRIBUTION:
1. DISTRIBUTION in the body .
2. conc of substance at specific body sites.

7. • BIOTRANSFORMATION ( B M ):
1. Efficiency of BM & Metabolic nature .
2. Substance ability (or) its metabolites pass
through cell membrane & contact with
specific cell components ex : DNA .
3. Amount and storage duration of Substance
/ metabolites in body tissues .
 EXCRETION : rate and EXCRETION site of
Substance .

8. • BIOTRANSFORMATION ( B M ):
1. Efficiency of BM & Metabolic nature .
2. Substance ability (or) its metabolites pass
through cell membrane & contact with specific
cell components ex : DNA .
3. Amount and storage duration of Substance /
metabolites in body tissues .
 EXCRETION : rate and EXCRETION site of
Substance .
 Age and health status of person exposed .

9. INTER –RELATED PROCESSES OF
ADME :
• Substance absorbed
• distributed
through blood ,lymph circulation ,ECF into
organs metabolized
• substance
/metabolites body waste products
• Excretion.

11. TK PARAMETERS :
1. AREA UNDER DRUG CONC CURVE :
• Plasma
AUC
Toxin
Conc
time

12. • AUC0
• ∞ Represents ( total amount of
toxin absorbed .
• Imp parameter ( how well toxin absorbed ).
• It is imp in FDA drug approval process .
2. VOLUME OF DISTRIBUTION ( Vd ):
I. Pure kinetic parameter .
II. Estimate degree of toxin parameter to the diff
fluid compartment of body .

13. • (VS )
iii. Vd = Amount of toxin in body
conc of toxin in blood /plasma.
DEGREE OF TOXIN
( 1 COMPARTMENT )
DIFFERENT FLUIDS
COMPARTMENT OF BODY
COMPARING

14. • 3 . CLEARANCE : rate of elimination
• conc
• Clearance of a toxin from a body .
• It may be expressed as a total body clearance.
• Clearance from a specific organ such as kidney
or plasma .
4. Plasma clearance : volume of plasma cleared of
toxin per unit time as a result of all elimination
pathways .

15. • RENAL CLERANCE :
• volume of plasma cleared of toxin by kidney per
unit time.
• PLASMA HALF LIFE :
•
• Plasma
• Conc 1 ½
time

16. • SINGLE ORGAN ELIMINATION:
• rate at which toxin is cleared from an organ
known as Elimination rate .
• EXTRACTION RATE :
• Difference between inlet conc and outlet conc
/inlet conc of an organ .
• Degree of toxin which is eliminated degraded
by that organ.

17. APPLICATIONS :
• TK methods are potential tools in human
health risk assessment .
• TECHNIQUES:
• 1.More precise scenario of drug kinetics and
metabolism.
• 2.Improved assessment strategy with greater
efficiency .
• 3.use fewer animals provide better data risk
assessment purposes.

18. • 4.develop pre- of drug response clinical
biomarkers and toxicity .
• 5.adoption of toxicity management approaches
and it improves therapeutic evaluation .
• 6.proactively screens /evaluate leads at early
stages using predictive tools for toxicity &MOA .
• 7.Rescue at risk programs in preclinical /early
clinical development .