Pharmacokinetics

Question 1

Metabolism involves phase I or II reactions. Describe the difference between the two types.

Answer 1

Phase I - oxidative and reductive reactions via cytochrome p450 system. Produces metabolites that RETAIN activity or that are ACTIVATED.

Phase II - conjugation reactions lead to INACTIVE metabolites that can be eliminated by biliary or renal excretion.

Question 2

AUC is a measure of what?

Answer 2

Area under the curve = a measure of total drug exposure

A drug is measured in plasma over time to generate a curve related drug concentration to time

Question 3

Name 2 classes of drugs for which the effect of the drug to cause killing of tumor cells or toxicity to normal tissues is DIRECTLY related to AUC

Answer 3

1. alkylating agents

2. cisplatin

Question 4

Name 3 classes of drugs for which the DURATION of exposure above a threshold concentration may be more important than AUC (ie weaker relationship bt AUC and drug effect)

Answer 4

1. Antimetabolites
2. Taxanes
3. Topo 1 inhibitors

Question 5

What is the formula for CLEARANCE

What is clearance an indicator of?

Answer 5

Cl = dose/AUC

Indicator of the RATE of ELIMINATION of the drug from the body and is expressed as a volume from which the drug is totally eliminated in a unit of time (usu ml/min)

Question 6

If clearance of a drug declines (ex. renal/hepatic dysfunction) then w/o dose adjustment, what happens to AUC and Drug Effect?

Answer 6

Both AUC and Drug effect with increase

Question 7

Volume of distribution

1. definition
2. what does a large Vd represent?

Answer 7

1. Vd: a hypothetical volume required to dissolve the total amount of drug at the same concentration as is found in blood immediately after injection
2. A large Vd represents extensive tissue binding! (ie vinca alkaloids)

Question 8

Half-life (t 1/2)

1. definition
2. what is it dependent on?
3. what will prolong t 1/2?

Answer 8

1. t 1/2 = the time required for the drug concentration in plasma to decrease by half
2. Is dependent on CLEARANCE (rate of drug elimination) and Vd
3. t 1/2 prolonged with large Vd and low clearance

Question 9

What is t 1/2 alpha? t 1/2 beta?

Which is more important?

Answer 9

t 1/2 alpha = distribution half-life

t 1/2 beta = elimination half-life = 0.693 Vd/clearance
**Beta more nb since most drugs undergo rapid distribution to tissues
For some drugs, may have slow phase of delayed elimination (ie removal of cisplatin bound to proteins)

Question 10

Steady state plasma drug concentration (Css)

1. definition
2. how many half lives?
3. determined solely by what and what?

Answer 10

Css

1. time at which the amount of drug being eliminated by body is equal to the amount of drug being added (plasma concentration remains constant)
2. roughly FIVE half-lives to reach steady state – > useful for designing CRIs
3. Css determined solely by RATE of drug infusion and CLEARANCE

Question 11

What is Cmax?

Answer 11

Cmax = peak plasma concentration