General Aspects of Pharmacokinetics

Question 1

What is clearance? How is it expressed?

Answer 1

parameter describing drug elimination defined as the volume of plasma which contains the total amount of drug that is removed from the body

volume per unit time; mL/min, L/hr

Question 2

What is clearance usually used to assess?

Answer 2

excretory capacity of an organ

Question 3

What is renal clearance? How is it calculated?

Answer 3

volume of plasma containing the amount of drug that is removed from the body by the kidneys

Question 4

What is the total body clearance?

Answer 4

sum of clearance rates for each mechanism involved in elimination of the drug

Question 5

Clearance is the proportionality factor to….

Answer 5

determine the rate of drug elimination

Question 6

Clearance does not describe….

Answer 6

the amount of drug being eliminated

Question 7

What is the rate of drug elimination?

Answer 7

amount of drug being eliminated per unit time

Question 8

How can overall clearance be estimated by measuring plasma concentrations at intervals following a single IV bolus dose (Q)?

Answer 8

AUC = area under the curve releating plasma concentration to time following a bolus dose

Question 9

How can drug clearance be determined in an individual subject by measuring the plasma concentration of the drug at intervals during a constant-rate IV infusion?

Answer 9

X = Css x CLtotal
CLtotal = x/Css

Question 10

What does a time curve during a constant IV infusion compare to following an IV bolus dose?

Answer 10

plasma concentration increases from zero to a steady state, and when the infusion is stopped, C declines to zero

plasma concentration rises abruptly and declines toward zero

Question 11

What is the elimination half-life of a drug?

Answer 11

the time necessary for plasma or blood concentrations to decline by 50%; disappearance of drug from plasma

Question 12

How many half-lives are necessary for a drug to be close to completely disappeared? What does it mean if a drug has a short half-life? Long?

Answer 12

by 5 half-lives, the drug will be 97% eliminated

the organ is rapidly clearing the drug
the drug persists within the body longer

Question 13

How do changes in volume of distribution affect half-life?

Answer 13

increases in volume of distribution increases the half-life of the drug and extends the duration of action of the drug and vice versa

Question 14

In what 3 clinical situations will the half-life of a drug increase? Decrease?

Answer 14

1. decreased renal or hepatic blood flow due to hemorrhage, heart failure, or cardiogenic shock
2. decreased renal function
3. decreased metabolism caused by another drug inhibiting biotransformation or hepatic insufficiency
4. increased hepatic blood flow
5. decreased protein binding so that drugs can more easily pass through the glomerulus
6. increased metabolism

Question 15

What is first-order elimination?

Answer 15

the same volume of blood will be irreversibly cleared of drug by an organ regardless of how much drug is in the blood (independent of PDC) - every unit of time, half of the drug will be eliminated

the half-life of a drug will be constant regardless of drug concentration

Question 16

Most drugs are eliminated using first-order elimination. When will drugs turn to zero-order elimination?

Answer 16

if the first-order elimination mechanisms become saturated due to a large concentration of drug present in the blood

(limited amount of enzymes and too much drug)

Question 17

What is zero-order elimination?`

Answer 17

the rate of elimination of a drug from the plasma is constant regardless of plasma concentration, however, the half-life is not meaningful and a set amount of drug is eliminated per unit time

Question 18

If a drug half-life is 2h, how long does it take the body to completely eliminate the drug?
a. 1 hr
b. 3 hr
c. 5 hr
d. 10 hr
e. 12 hr

Answer 18

E

2 hr = 50% of drug gone = 1 T1/2
5 T1/2 = most of drug gone
5 T1/2 = 10 hrs
10 + 2 = 12 hrs

Question 19

Assume a dog has ingested several aspirin to the point that the PDC has surpassed the therapeutic range of 100-500 mg/mL and has achieved the toxic concentration of 2000 mg/mL. The half life of aspirin is 9 hours.

a. Assume it is eliminated by first-order elimination. What will the concentration be at by 36 hours?
b. Assume it is eliminated by zero-order elimination at 100 mg/mL of aspirin per unit time. What will the concentration be at by 36 hours?

Answer 19

a. FIRST-ORDER = half-life/time (50% aspirin/9 hrs)
2000 —> 1000 —> 500 —> 250 —> 125 mg/mL aspirin (safe!)

b. ZERO-ORDER = constant amount eliminated per unit time (100mg/mL /9hrs)
2000 —> 1900 —> 1800 —> 1700 —> 1600 mg/mL aspirin (still toxic!)

Question 20

What common drug is eliminated using zero-order elimination?

Answer 20

the rate of elimination of ethanol from the plasma is constant, regardless of the dose or plasma concentration of the ethanol

Question 21

True or false: In first-order kinetic elimination, the drug’s half-life decreases with time

Answer 21

FALSE - half-life remains constant

Question 22

True or False: Drugs slowly eliminated require more frequent dosing.

Answer 22

FALSE

Question 23

What 4 things does understanding pharmacokinetics help us do in clinical practice?

Answer 23

1. interpret drug concentration
2. adjust dose regimens rationally
3. identify and evaluate possible drug interactions
4. individualize dose regimen when dealing with a severely ill patient

Question 24

In practice, pharmacokinetics focuses on what? What is therapeutic drug monitoring?

Answer 24

concentration of blood in the plasma, which allows for the individualization of dosages

achieving the desired therapeutic effect while minimizing adverse effects in each individual patient

Question 25

What is pharmacokinetic modeling? What is its purpose?

Answer 25

when a drug of interest is given as a single dose and drug concentrations are collected over time, usually for at least 3 elimination half-lives to ensure that all phases of the drug movement are identified

predict the behavior of a drug in the body

Question 26

How should a drug be administered for bioavailability studies using pharmacokinetic modeling?

Answer 26

intravenously as well as the route of interest

Question 27

What is the one compartment (single) model for pharmacokinetic modeling? When is this model applicable? While it is useful, what should be considered?

Answer 27

the body is considered as a single homogenous compartment - the entire dose of a drug is assumed to move out of the body at a single rate

if plasma concentrations fall exponentially after drug administration

it is a physiological oversimplification, since the different parts of the body are quite different in terms of blood supply

Question 28

What is the two-compartment model of pharmacokinetic modeling? Why is this usually used in pharmacology studied? What 2 things should still be considered?

Answer 28

model introduced another (peripheral) compartment to represent tissues in communication with the central plasma concentration

it resembles more closely to the real situation

1. this model still uses an approximation by lumping all organs and tissues in the peripheral compartment
2. this model assumes that drug molecules can only enter or leave the peripheral compartment through the central (plasma) compartment

Question 29

When is the multicompartment model used? What is the third compartment considered?

Answer 29

experiments conducted over long time frames or in production animals

tissue residue of the drug in a food-producing animal’s product (meat, milk, etc.)