Toxicokinetics

Question 1

Toxicity

Answer 1

a measure of the degree to which something is toxic or poisonous

Question 2

Xenobiotic

Answer 2

Compound with a chemical structure foreign to a given organism

Question 3

Factors affecting response to toxic chemical

Answer 3

he substance
* Dose (dose-response)
* Uptake into the body (absorption)
* Movement within the body (distribution)
* [Accumulation]
* Chemical conversion to non-toxic or toxic substance (metabolism) * Removal from the body (excretion)

Question 4

One-compartmental model

Answer 4

Xenobiotic distributes into a single, homogenous “vessel”

Question 5

n- compartment model

Answer 5

Xenobiotic distributes into a central, and then to one ore more peripheral compartments.

Question 6

Thermodynamic

Answer 6

Involves the relationship between total concentration of xenobiotic in tissue and the free concentration within the tissue
* Assumes equilibrium between total and free xenobiotic
* Only free is available for binding, metabolism or removal from the
tissue by blood
* Need to know partition or distribution coefficients for calculations

Question 7

First-pass metabolism

Answer 7

Process of biotransformation of xenobiotic before reaching systemic circulation
Small intestine and liver

Question 8

Bioavailability

Answer 8

The actual extent of exposure as defined by the amount of toxicant reaching the systemic circulation is determined by (1) entry barrier permeability, and (2) the extent of “first-pass” metabolism
* The fraction of dose reaching the system circulation in intact form, or systemic availability (F), is estimated from the AUCs,

Question 9

Vd

Answer 9

Apparent volume of distribution

Question 10

ke

Answer 10

Total elimination rate constant

Question 11

Apparent volume of distribution(Vd)

Answer 11

space in which an amount of chemical is distributed in the body to result in a given plasma concentration
Total amount of drug in the body/drug blood plasma concentration
X/c

Question 12

Total elimination rate constant, k [h-1]

Answer 12

The fraction of xenobiotic eliminated per unit time

Question 13

Elimination from: Metabolism

Answer 13

Km

Question 14

Elimination from: Kidneys

Answer 14

kr

Question 15

Elimination from: Lungs

Answer 15

kx

Question 16

ke =

Answer 16

km + kr +kx

Question 17

Elimination rate, -dX/dt [mg h-1]

Answer 17

the rate at which xenobiotics are removed from the system

Question 18

X

Answer 18

amount of xenobiotic

Question 19

First order elimination

Answer 19

Amount of xenobiotic eliminated is proportional to the concentration of xenobiotic in plasma
- dC/dt = k * c e

Question 20

c

Answer 20

concentration of xenobiotic

Question 21

What is the concentration of a xenobiotic at a given time..?

Answer 21

ct = co * e^-ke*t

Question 22

co

Answer 22

initial concentration (at time 0)

Question 23

ln Ct =

Answer 23

• ke * t + ln C0

Question 24

ke =

Answer 24

ln C0 - ln Ct / t – t0

Question 25

Half life, t1/2

Answer 25

The half-life of elimination t1/2 is the time required for the blood or plasma xenobiotic concentration to decrease by one-half (and is dependent on both volume of distribution and clearance)…

Question 26

t1/2 =

Answer 26

ln2 / ke = 0.693 / ke

Question 27

First order kinetics

Answer 27

For first order elimination, the rate at which a chemical is eliminated at any time is directly proportional to the amount of that chemical in the body at that time
Concentration of chemical in plasma and other tissues decreases similarly by some constant fraction per unit of time, the elimination rate constant, ke

Question 28

One – compartment model

Answer 28

first order kinetics
xenobiotic distributes into a single, homogenous “vessel”

Question 29

Zero order elimination

Answer 29

• dC/dt = constant
  Rate or amount of chemical eliminated at any time is independent of the amount of chemical in the body
  For zero order processes, the arithmetic plot of plasma conc. vs time yields a straight line
  A true t1/2 or ke does not exist but differs depending on the dose