T2 - Measurement of Drug Concentrations in Biological Specimen T2 Flashcards
What is the purpose of the correlation between drug concentration measurements and pharmacodynamic outcomes?
To optimize pharmacodynamic responses
How is drug concentrations collected if it is difficult to measure at the site of drug action?
Measured by surrogate biological samples like milk, saliva, plasma, urine, feces, tissues
What happens if [drug] is collected in tissues?
May not reflect [drug] in other tissues
What if [drug] is collected in urine?
It is an indirect method to ascertain the bioavailability of a drug
How is [drug] effected when collected as feces?
Drugs in feces reflect unabsorbed drug after an oral dose or drug expelled by biliary secretion after systemic absorption
What if [drug] is collected by saliva?
Free drug diffuse into saliva and tends to approximate free drug plasma concentration
What are the most common and direct approaches to assessing pharmacokinetics?
Measurement of drug and metabolite concentrations in the serum or plasma
How is serum obtained?
When whole blood is allowed to clot and after centrifugation, the supernatant is serum
How is plasma obtained?
From the supernatant of centrifuged whole blood to which an anticoagulant has been added
Is the plasma content of serum and plasma the same?
No
Why do we measure [drug] in plasma?
- Drug in the plasma is in dynamic equilibrium with the tissues
- Drug in the plasma are bound to plasma proteins
- To monitor plasma drug concentrations
Describe the equilibrium of drug concentrations between plasma and tissues?
- Plasma [drug] are good predictors of tissue [drug] but not identical
- Changes in plasma [drug] reflect the changes of tissue [drug]
Describe the differences of measuring bound and unbound [drug]?
- Plasma protein bound can be used to measure total drug concentrration
- Free (unbound) [drug] is measured after filtration
What is the purpose of monitoring plasma drug concentrations?
- Allows adjustment of drug dosage → to individualize and optimize therapeutic drug regimens based on PK parameters
- Provides a guide to modify the drug dosage with disease progression as PH parameters change progressively as many disease states progress, when alterations in physiologic functions occur
Why should we predict drug concentration at any time after drug dose?
- Quite often plasma drug concentrations are good predictors of drug concentration in tissues including sites of drug actions - they can be used for dose optimization.
- But drug concentrations in plasma and tissues are not identical.
What does the Cmax represent?
The observed peak concentration of a drug in the plasma
What does the Tmax represent?
Time of peak concentration of drug in plasma
What does the Area under the curve (AUC) represent?
The total amount of drug absorbed into the circulation
What are the components the time curve?
A: Peak concentration (Cmax)
B: AUC
C: Peak time (Tmax)
What are the components of the time curve?
A: Peak level
B: Onset
C: Therapeutic window
D: Mainly metabolism and excretion
E: Mainly absorption
F: Lag
G: Duration of effect
H: Threshold for toxic effect
I: Toxic region
J: Threshold for desired effects
What are the characteristics of the absorption rate?
Cmax and Tmax
What affects the Cmax and Tmax?
Drug dissolution and release of dosage form
Why are Cmax and Tmax not used as pure measures of the absorption rate?
They are single-point estimates and doesn’t account for all data sampled during the absorption process
What make Cmax clinically relevant?
Peak plasma concentration is related to maximal pharmacological effects or adverse effects
What is AUC used for?
- To evaluate the extent of absorption
- Used to compare bioavailability differences between
a. Brand and generics of drugs of the same dosage form
b. Different dosage forms of a drug
What factors affects AUC?
Formulation for the dosage form
What factors play into AUC?
- Bioavailability
- Systemic drug clearance
- Dose
- AUC = Dose/CL
What does this curve indicate?
- No drug absorption involved in IV bolus
- Assumes drug distribution is instantaneous (the moment it’s injected
- Distribution is non-existent
- Represents metabolism + excretion
What do these curves indicate?
- Occurrence of drug absorption until Cmax is achieved
- Drug then undergoes disposition (distribution+elimination+excretion) slower paces that absorption
Which of the graphs has the slowest absorption?
Rectal. The longer (wider) the Tmax the slower the absorption
Which of the graphs has the faster absorption?
Inhalation, the curve is closer to y-axis.
What do these curves indicate?
1., IV infusion, drug absorption is slower and tmax is delayed and disposition (distribution+elimination) declines slowly
2. IV infusion is continuing to rise
