The ultimate goal of pharmacokinetics is ________
to identify a dosing regimen that is safe, effective, and devoid of unintended consequences
What was AMDUCA?
Animal Medicinal Drug Use and Clarification Act of 1994
Allowed for greater flexibility in therapeutic dosing regimens and new uses in non-approved species
Key pharmacokinectic properties of a drug
- volume of distribution (VD)
- Clearance (Q)
- Elimination Half Life (T1/2)
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%
Factors for low bioavailability
- 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
First Pass metabolism
drug is ingested, enters portal vein, and is metabolized in liver; greatly reduces amount of drug that enters the systemic circulation
What routes of administration bypass first pass metabolism?
Under the tongue, IV, direct injection, or suppository
The greatest interspecies differences in bioavailability occur with __________
For oral drugs, disruption of GI epithelia will increase/decrease bioavailability?
increase (e.g. parvovirus)
When working with the volume of distribution, there's an assumption that the plasma concentration of the drug is the same as what?
the tissue concentration
Conditions affecting VD
- 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
Zero Order Kinetics
fixed (constant) rate of elimination that is not related to drug concentration; fixed amount of drug is eliminated per unit time
First Order Kinetics
exponential rate of elimination that is proportional to drug concentration; fixed fraction of drug is eliminated per unit time (e.g. most drugs)
What does the slope of the line of a semi-log plot represent?
the rate of drug elimination (KE); more common for drug elimination
What does the slope represent in a linear plot?
it is proportional to the drug concentration at that time; drug decreases exponentially
Half life (T1/2)
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 (KE)
KE = 0.693/T1/2
After how many half lives would the drug concentration be below therapeutic threshold and lack desired effect?