Important Pharmacokinetic Parameters

How many half-lives would it take for 99% of a dose of drug to be eliminated from plasma?

7

1 half-life: 50%

2 half-life: 25% (75% eliminated)

3 half-life: 12.5

4 half-life: 6.25

5 half-life: 3.125

6 half-life: 1.5625

7 half-life: 0.78125 (99.9% eliminated)

First-order vs zero-order elimination

Volume of distribution (Vd)

Clearance (Cl)Elimination half-life (t1/2)

Steady state

We assume most drugs undergo _______ order elimination

first

What is first order elimination of a drug?

a log-linear or constant proportion is eliminated per unit time

What is zero order elimination of a drug?

a constant amount of drug is eliminated per unit time, which is often the elimination behavior of toxins

__________ is the volume of plasma completely cleared of drug per unit time (usually minutes or hours)

Clearance

What is volume of distribution?

the amount of drug in the body divided by the concentration measured in plasma

Complete this principle of pharmacology: Volume of distribution can vary with _______ (and other animal factors) and it does vary with ________

age

drug

What two pharmacological parameters can be used to calculate the rate of elimination or elimination half-life?

Clearance

Volume of Distribution

A larger volume of distribution of a drug would result in that drug having a _________ rate of elimination (half-life)

larger/longer

A smaller volume of distribution of a drug would result in that drug having a _________ rate of elimination (half-life)

smaller/shorter

A smaller clearance of a drug would result in that drug having a _________ rate of elimination (half-life)

larger/longer

A larger clearance a drug would result in that drug having a _________ rate of elimination (half-life)

smaller/shorter

You are evaluating an experiment that examined the IV pharmacokinetic characteristics of two drugs, Drug A and Drug B. If the two drugs have the same concentrations at every time point you collected samples, but you calculate that the volume of distribution of Drug A is larger than Drug B, how can this be explained?

a) You administered more milligrams of Drug A than Drug B

b) You administered more milligrams of Drug B than Drug A

c) The bioavailability of Drug A is higher than Drug B

d) The bioavailability of Drug B is higher than Drug A

a) You administered more milligrams of Drug A than Drug B

(look back at equation for volume of distribution, Vd = (amt drug in body/[drug measured in plasma])

What is steady state?

steady state occurs when the amount of drug administered to an animals is equal to the amount being eliminated

Complete this principle of pharmacology: Time to steady state is not the same as time to therapeutic ______________

concentrations

Steady state is typically used to describe drugs that we administer __________

chronically

Rule of thumb: time to steady state is related to elimination half-life only (so Vd and Cl) - it takes approximately ____ half-lives to be close to steady state

5

Complete this principle pharmacology: Therapeutic concentrations can be reached in drugs with long half-life by using __________ dose

loading

If the dose is increased (or the rate of infusion in increased), the concentration at steady state will increase, but not the ________ to reach steady state

time