W8.1_Introduction to Pharmacokinetics

Question 1

Define pharmacokinetics. What are the clinical points of measurements in pharmacokinetics? What would be the basic questions of it?

Answer 1

• Definition: what the body does to the drug
• Clinical endpoints: measuring drug amount/concentration in biological spaces and fluids at specific time
• Where, how much, when does the drug go?

Question 2

According to the cumulative amount of drug excreted versus time profile in urine or faeces, how can different drug concentrations in plasma be measured? What is the subsequent step?

Answer 2

• Measuring drug concentration in plasma
• LC-MS (liquid chromatography-mass spectrometry) for small molecule drugs
• Immunoassay (ligand binding assay) for antibody drugs
• After measuring -> calibration curve for quantification

Question 3

According to the pharmacokinetic profile, define therapeutic range, Cmax, Tmax, AUC, and t1/2. How can the route of administration be determined from it?

Answer 3

• Therapeutic range: between MTC (maximum tolerated concentration) and MEC (minimum effective concentration)
• Too low: no treatment effect vs too high: toxicity/ADR
• Cmax: peak/maximum concentration (µg/mL)
• Tmax: time required to reach Cmax (hr)
• AUC: area under curve = total drug exposure across time (used to calculate bioavailability) (µg⋅h/mL)
• t1/2: half-life is the time taken for drug concentration in plasma to reduce by half (used to determine distribution and elimination) (hr)
• Route of administration can be determined by looking at the profile (X absorption? flat/steep? lag time?)

Question 4

What are the typical phases in a pharmacokinetic profile? Are there any exceptions? What is the use of pharmacokinetics in a clinical setting?

Answer 4

• 0 -> onset time: absorption lag time
• Onset time -> Tmax: absorption phase
• Tmax -> 0: elimination phase
• Exception: prolonged-release drugs (phases overlap and hard to distinguish)
• Use of pharmacokinetics: dose adjustment for renal repairment

Question 5

Contrast pharmacokinetic and pharmacodynamic variabilities by giving examples.

Answer 5

Pharmacokinetic variability
- Compliance
- Dosing or medication errors
- Tissue and body fluid mass and volume
- Drug interactions
Pharmacodynamic variability
- Drug receptor status
- Genetic factors
- Drug interactions
- Tolerance