Drug Distribution Flashcards
Describe the difference between zero and first order pharmacokinetics.
Most drugs obey first order kinetics:
- A constant fraction of drug is removed in a given duration
- The time taken to remove the drug is independent of dose
- The drug has a constant half-life
A few drugs obey zero order kinetics:
- A constant amount of drug is removed in a given duration
- The bigger the dose, the longer the time taken to remove it
- I.e. absorption, distribution, elimination processes saturated
- At low dose no saturation - return to first order
Name 2 drugs that obey zero order kinetics.
Alcohol, phenytoin
What is apparent volume of distribution? Name 2 factors that influence it.
- Vd = total amount of drug / [drug in plasma]
- If Vd > 4-5, some volume must be distributed outside circulation - i.e. extravascular space
- Vd influenced by:
- Lipid/water solubility
- Binding to plasma proteins
What is the bioavailability of a drug?
- Bioavailability, F = fraction of drug in circulation compared to dose
- Bioavailability measures extent of absorption
- If F = 0.1 > bioavailability = 10%
Describe 3 factors responsible for low bioavailability.
- Poor absorption
- Chemical reactions at site of delivery
- First-pass metabolism - drug is highly metabolised in liver before reaching circulation
Explain the principle of steady state dosing.
- Equilibrium of dosing rate with elimination rate
- Aim is to reach steady state within therapeutic window of drug - i.e. at the ideal concentration
- Dosing rate x F = CL x target concentration
- Takes 4-5 half-lives to reach steady state
Describe how dosing rate can be calculated.
- Dosing rate x bioavailability (F) = clearance (CL) x target concentration
- F = 1 if drug given i.v.
When targeting steady state dosing, why should fluctuations in concentration be minimised and how is this achieved?
- Fluctuations create the potential for sub-optimal treatment or toxicity
- Fluctuations can be minimised by giving more frequent, smaller doses
What is a loading dose?
- Loading dose - an initial higher dose given at the start of treatment
- A maintenance dose is then used to keep the drug at steady state
- Giving a loading dose accelerates the achievement of steady state for drugs with a long half-life
Will changing the rate of drug infusion change the time required to reach steady state?
No, changing the dosage will only change the concentration achieved at steady state. The time taken to reach steady state is always 4-5 half-lives.
A drug with a half-life of 4 hours reaches an initial blood concentration of 16mg/ml. Assuming first-order kinetics, what is the drug concentration after 16 hours?
- 16h = 4 half-lives, thus
- Concentration = 16 / 24 = 1mg/ml
