Ch 5 Absorption Distribution and Excretion of Toxicants
Unit 2 – Disposition of Toxicants
Ch 5 – Absorption, Distribution, and Excretion of
Toxicants
Ch 7 - Toxicokinetics
Chapter 5 Absorptions, Distribution, and Excretion of
Toxicants
© The McGraw-Hill Companies, Inc, 2011
Factors Affecting Disposition
• If fraction absorbed or rate absorbed is low, may never reach high enough concentration to cause toxicity
• Concentrated in a tissue other than the target organ, thus decreasing toxicity
• Biotransformation may result in formation of less toxic or more toxic metabolites
• Rapid elimination will result in lower concentration and hence its toxicity in target tissues.
TOXICODYNAMICS
TOXICOKINETICS
EXPOSURE to TOXICANT
ABSORPTION
CELL TOXICITY
DISTRIBUTION
BIOTRANSFORMATION
ELIMINATION
STORAGE
Pharmacokinetics
• The quantitative study of the metabolic processes of absorption, distribution, biotransformation and elimination Purpose:
• Predict body burdens - both time to maximum and amount • Predict duration in body after exposure is terminated
• Determine percent absorbed
• Determine schedule of drug dosage
Zero-Order and First-Order Kinetics
Zero-Order Process
Characteristics.
• Rate remains constant and is independent of concentration or amount of chemical
• The biological system is rate limiting
• T½ increases with dose (not a true T½)
Example: body can metabolize 10 ml/hr of ethanol which is 1 beer or 1 mixed drink per hour. Thus, if you drink a six pack of beer in one hour the following kinetics would occur:
Zero-Order process
TIME (HR)
0
1
2
3
4
5
6
--------------------------------------------------------------------------------------------------------------------------------------------------
Ethanol Remaining (ml)
60 50 40 30 20 10 0
Ethanol Eliminated (ml)
0
Ethanol Eliminated
(% removal)
0
10 10 10 10 10 10
17 20 25 33 50 100
-------------------------------------------------------------------------------------------------------------------------------------
First-Order
Ch 5 – Absorption, Distribution, and Excretion of
Toxicants
Ch 7 - Toxicokinetics
Chapter 5 Absorptions, Distribution, and Excretion of
Toxicants
© The McGraw-Hill Companies, Inc, 2011
Factors Affecting Disposition
• If fraction absorbed or rate absorbed is low, may never reach high enough concentration to cause toxicity
• Concentrated in a tissue other than the target organ, thus decreasing toxicity
• Biotransformation may result in formation of less toxic or more toxic metabolites
• Rapid elimination will result in lower concentration and hence its toxicity in target tissues.
TOXICODYNAMICS
TOXICOKINETICS
EXPOSURE to TOXICANT
ABSORPTION
CELL TOXICITY
DISTRIBUTION
BIOTRANSFORMATION
ELIMINATION
STORAGE
Pharmacokinetics
• The quantitative study of the metabolic processes of absorption, distribution, biotransformation and elimination Purpose:
• Predict body burdens - both time to maximum and amount • Predict duration in body after exposure is terminated
• Determine percent absorbed
• Determine schedule of drug dosage
Zero-Order and First-Order Kinetics
Zero-Order Process
Characteristics.
• Rate remains constant and is independent of concentration or amount of chemical
• The biological system is rate limiting
• T½ increases with dose (not a true T½)
Example: body can metabolize 10 ml/hr of ethanol which is 1 beer or 1 mixed drink per hour. Thus, if you drink a six pack of beer in one hour the following kinetics would occur:
Zero-Order process
TIME (HR)
0
1
2
3
4
5
6
--------------------------------------------------------------------------------------------------------------------------------------------------
Ethanol Remaining (ml)
60 50 40 30 20 10 0
Ethanol Eliminated (ml)
0
Ethanol Eliminated
(% removal)
0
10 10 10 10 10 10
17 20 25 33 50 100
-------------------------------------------------------------------------------------------------------------------------------------
First-Order