Basic Toxicokinetics

Question 1

What is classical toxicokinetics based on?

Answer 1

Mathematical models or compartments, usually only 1

or two compartment models. Uses classical kinetics, Vd, Km, AUC

Question 2

What is physiologically based toxicokinetics based on?

Answer 2

Physiological compartments - measured blood

flows and anatomic, physiological, thermodynamic, and transport parameters

Question 3

Difference between Toxicokinetics and Toxicodynamics?

Answer 3

Toxicokinetics: rate at which events occur.
- ADME
Toxicodynamics: physiological response from the exposure or health effect.
- Bio activation, cellular changes, cytoprotection

Question 4

What is pharmacokinetics (toxicokinetics)?

Answer 4

Study of absorption, distribution, metabolism and excretion of xenobiotic in whole animal

Question 5

What is pharmacodynamics (toxicodynamics)?

Answer 5

Study of toxicological effects of the xenobiotic at the target site in whole animals

Question 6

Classical toxicokinetics (summary)?

Answer 6

1. .) Based on observed data
2. ) Utilize one or two compartment models
3. ) Do NOT require any prior knowledge of anatomy/physiology
4. ) Provide usefull preliminary data on xenobiotic toxicity in humans

Question 7

What is bioavailability?

Answer 7

A substance may be very toxic but if it is not “bioavailable” it poses little risk to the individual**

1. .) Toxicity is dependent on dose delivered to the target organ/site
2. ) Physical properties of xenobiotic determine bioavailability
3. ) Determined by comparing AUC of the test route of exposure to the AUC of an iv dose

Question 8

What is an important factor when dealing with periodic exposure?

Answer 8

Accumulation, such as at the workplace.

Question 9

What is saturation toxicokinetics?

Answer 9

As dose increases, processes can be exceeded and saturation occurs (Michalis Menton kinetics). Can result in buildup of toxic metabolite at high concentrations (i.e. Ethanol, Styrene)

Question 10

What is half-life (T1/2)?

Answer 10

Time required for blood/plasma concentration to decrease by 1/2. Dependent on Vd and clearance.

Question 11

What is clearance?

Answer 11

The rate of chemical elimination from the body or compartment. Expressed as mL eliminated/min, total clearance = sum of individual clearances.

Question 12

What concept is related to how fast a chemical is removed from the body?

Answer 12

Clearance**

Question 13

What is Area Under the Curve (AUC)?

Answer 13

Integrated concentration from zero - infinity versus time