L2 Pharmacokinetics I: Absorption and Distribution Flashcards
(40 cards)
___ is the time course of drug action as it relates to the concentration of the drug in the plasma.
Pharmacokinetics
What are the four major aspects of pharmacokinetics?
ADME:
- Absorption
- Distribution
- Metabolism
- Excretion
With respect to the time course of plasma drug concentration, when does the onset occur?
The onset occurs when the drug reaches the minimum effective concentration.
With respect to the time course of plasma drug concentration, what is the duration?
The time from onset to the time the drug drops below the minimum effective concentration
With respect to the time course of plasma drug concentration, what is the intensity?
The concentration between the minimum effective concentration and the maximum concentration reached
With respect to the time course of plasma drug concentration, what is the therapeutic range?
Maximum tolerated concentration to minimum effective concentration
AUC = ? (for i.v.)
Dose (i.v.) / CL
CL = clearance
AUC = ? (for p.o.)
DOSE (p.o.) / (CL/F)
CL = clearance F = bioavailability
What are the two major uses of the AUC?
- Compare amount of drug that reaches the systemic circulation by different routes of administration (bioavailability)
- Compare clearance of a drug in different individuals after administration of the same dose
F = ?
AUC oral/AUC i.v. (%)
CLx/CLy = ?
AUCy/AUCx
What is the process by which drugs move from their site of administration to the plasma?
Drug absorption
What are some factors that affect drug absorption?
- Chemical composition of drug and delivery formulation
- Regional differences in blood flow
- Transport mechanisms
- Permeability characteristics
- Ion-trapping
- Non-specific binding
- Surface area
Lipid solubility is affected by the degree of ___.
Ionization
pKa = ?
Acids: pH + log[AH]/[A-]
bases: pH + log [BH+]/[B}
Weak acids are non-ionized most in ___ environments such as the ___; weak bases are non-ionized most in ___ environments such as the ___.
Acidic; stomach; basic; small intestine
What is the main site of absorption of most orally administered drugs and why?
Small intestine; much larger surface area than the stomach.
What are the three major processes that reduce bioavailability?
- First-pass metabolism
- Secretion into bile and reabsorption into the intestine
- Incomplete absorption
What is the fraction (F) of the administered dose that reaches the systemic circulation in its active form?
Bioavailability
F oral = ?
AUC p.o. / AUC i.v.
Dose p.o. = ?
Dose i.v. / F oral
What is the salt factor (S)?
The fraction of the total drug that will be delivered as active drug to the systemic circulation when a fraction of the total weight is inactive salt
What must be adjusted by the salt factor to achieve a specific target concentration of the active drug?
Loading or maintenance doses (multiply F by S)
What are the advantages and disadvantages to sublingual and buccal drug administration?
Advantages: avoids first pass metabolism, higher pH better for absorption of basic drugs
Disadvantages: taste and discomfort
