Toxicokinetics Flashcards
(16 cards)
What factors influence the rate and extent of absorption of a chemical into systemic circulation?
Factors include:
* Dose
* Exposure route
* Volume and type of exposure matrix or dosing vehicle
The rate and efficiency of crossing biological membrane barriers are also crucial.
What does a value of F < 1 indicate in toxicokinetic studies?
It indicates that less than 100% of the administered dose reaches the systemic circulation.
F is the bioavailability calculated from AUC values.
What is the volume of distribution (Vd)?
Vd corresponds to the apparent volume of a biological fluid in which a xenobiotic is diluted, expressed in mL or L.
It reflects how a chemical distributes in the body.
What does a high volume of distribution (Vd) indicate?
It indicates a substance has a marked affinity for tissue or fat depots, leading to low plasma concentrations.
Vd can exceed physiological fluid spaces and body weight.
Define clearance (CL) in toxicokinetics.
Clearance (CL) is the apparent volume of a physiological fluid cleaned of a toxicant per unit time (mL/min or L/h).
High CL values indicate efficient removal from systemic circulation.
What is the relationship between CL and AUC?
An inverse relationship exists; lower CL results in higher AUC and greater systemic exposure to the parent chemical.
AUC is the area under the concentration versus time curve.
What does elimination half-life (t1/2) represent?
t1/2 is the time taken for the concentration of a chemical in a biological matrix to be reduced by half.
It is influenced by both Vd and CL.
What is the elimination rate constant (Kel)?
Kel represents the fraction of the chemical removed from systemic circulation per unit time.
It is used to calculate the elimination half-life.
What does a one-compartment toxicokinetic model represent?
It represents the body as a homogeneous system with uniform distribution of a chemical.
The model simplifies analysis of toxicokinetics.
What is the mathematical representation of the one-compartment model rate of change?
dAmountbody/dt = Doseabsorbed - Amounteliminated
Abody is the amount in the body, Ka is the absorption rate constant, and Kel is the elimination rate constant.
What do the coefficients A and B represent in a biexponential equation?
A and B are coefficients in units of toxicant concentration for the distribution and elimination phases, respectively.
They help describe the kinetic behavior of a toxicant.
In a two-compartment model, how is clearance (CL) calculated?
CL is equal to Vd times β.
β is the elimination rate constant for the peripheral compartment.
What does a straight line in log-transformed concentration versus time plots indicate?
It indicates that a one-compartment model fits the concentration data.
This is used to derive toxicokinetic parameters.
What is the formula for calculating the elimination half-life (t1/2) from the elimination rate constant (Kel)?
t1/2 = 0.693 / Kel
This formula is derived from the properties of first-order kinetics.
What is the significance of the area under the concentration-time curve (AUC)?
AUC is crucial for determining bioavailability and systemic exposure to a toxicant.
It reflects the total drug exposure over time.
True or False: Elimination occurs only after distribution is complete in a two-compartment model.
False
Elimination occurs during both distribution and elimination phases.
