Clinical Applications of Pharmacokinetics

Question 1

The ultimate goal of pharmacokinetics is ________

Answer 1

to identify a dosing regimen that is safe, effective, and devoid of unintended consequences

Question 2

What was AMDUCA?

Answer 2

Animal Medicinal Drug Use and Clarification Act of 1994

Allowed for greater flexibility in therapeutic dosing regimens and new uses in non-approved species

Question 3

Key pharmacokinectic properties of a drug

Answer 3

• bioavailability
• volume of distribution (V_D)
• Clearance (Q)
• Elimination Half Life (T_1/2)

Question 4

Bioavailability (F)

Answer 4

the fraction of drug absorbed into circulation

F = AUC oral/AUC IV X 100

*curve represents the extent of absorption; for IV it should be 100%

Question 5

Factors for low bioavailability

Answer 5

• large molecule size
• highly polar drug
• drug binding to dietary cationic minerals
• degradation by stomach acid, duodenal bacteria, or brush border enzymes
• high tranporter efflux
• high degree of intestinal and/or hepatic biotransformation to inactive metabolites
• decreased blood flow/sepsis

Question 6

First Pass metabolism

Answer 6

drug is ingested, enters portal vein, and is metabolized in liver; greatly reduces amount of drug that enters the systemic circulation

Question 7

What routes of administration bypass first pass metabolism?

Answer 7

Under the tongue, IV, direct injection, or suppository

Question 8

The greatest interspecies differences in bioavailability occur with __________

Answer 8

oral administration

Question 9

For oral drugs, disruption of GI epithelia will increase/decrease bioavailability?

Answer 9

increase (e.g. parvovirus)

Question 10

When working with the volume of distribution, there’s an assumption that the plasma concentration of the drug is the same as what?

Answer 10

the tissue concentration

Question 11

Conditions affecting V_D

Answer 11

• Ascites can increase, due to decreased binding proteins in the plasma
• Obesity can increase, due to more adipose tissue to bind to
• Dehydration can decrease
• Pancreatitis decreases it for certain drugs b/c cells get destroyed

Question 12

Zero Order Kinetics

Answer 12

fixed (constant) rate of elimination that is not related to drug concentration; fixed amount of drug is eliminated per unit time

Question 13

First Order Kinetics

Answer 13

exponential rate of elimination that is proportional to drug concentration; fixed fraction of drug is eliminated per unit time (e.g. most drugs)

Question 14

What does the slope of the line of a semi-log plot represent?

Answer 14

the rate of drug elimination (K_E); more common for drug elimination

Question 15

What does the slope represent in a linear plot?

Answer 15

it is proportional to the drug concentration at that time; drug decreases exponentially

Question 16

Half life (T_1/2)

Answer 16

time required to eliminate 1/2 of the drug in the plasma; constant for drugs that show first order kinetics; is inversely proportional to the elimination rate constant (K_E)

K_E = 0.693/T_1/2

Question 17

After how many half lives would the drug concentration be below therapeutic threshold and lack desired effect?

Answer 17

5