Unit 2 - ADME - PK Flashcards
What does pharmacokinetics describe?
The relationship between dose and concentration
- changes with time
What underpins the relationship between dose and therapeutic benefit?
Pharmacokinetics
- how body manages drug
Pharmacodynamics
- how the drug affects the body
What physiochemical properties underpin pharmacokinetics and pharmacodynamics to determine patient outcomes?
Solubility in biological fluid Permeation across biological barriers Metabolism by enzyme Secretion by transporters Interaction with pharmacologic receptor
What is ADME?
Mechanisms of how drugs interact with, and are handled by, the body
- absorption
- distribution
- elimination
- metabolism
- excretion
What is Absorption in ADME?
Process by which unchanged drug proceeds from ‘absorptive barrier’ to circulatory system
What is Distribution in ADME?
Process of drug transfer from immediate post-absorption site to tissues
What is Elimination in ADME?
Process of irreversible loss of drug from the body via
- metabolism
- excretion
What is pharmacokinetics?
Quantitative descriptors determined from plasma drug concentration vs time profiles which are used to characterise the drug and predict outcome of drug administration
- clearance of drug from body (CL)
- volume of distribution of drug within body (V)
- elimination half life (T1/2) of drug from body
- bioavailability (F)
- fractional availability of dose
- 0 - 1
What is Disposition in ADME?
Distribution
Metabolism
Excretion
What types of biological barriers do drugs need to cross?
Plasma membranes - lots of different types Epithelium - intestinal cells - enterocytes Capillary endothelium of vascular beds - different types - GI tract - Blood Brain Barrier - respiratory system Transporters Enzymes Protein binding
Which processes occur concurrently in the body?
ADME
Give examples of formulations which are taken orally?
Tablets
Capsules
Emulsions
Suspensions
What are oral formulations subjected to?
Hepatic first pass metabolism before distribution
- absorbed into GI tract
Give examples of formulations that enter the bloodstream via the respiratory system
Spray
pMDI
DPI
Nebuliser
Give examples of formulations that enter the bloodstream via the skin
Patch
Cream
Ointment
Microneedles
Give examples of formulations that enter the bloodstream directly
Implants - release drug over time Intravenous injection Intramuscular injection Subcutaneous injection Intradermal injection
What role does the circulatory system play regarding ADME?
Distribution of drugs around the body
- opportunity to reach target
- interact with tissues
- be eliminated
What does a single IV bolus concentration-time profile show?
No absorption phase Disposition only - Distribution - Metabolism - Excretion
What does a continuous IV infusion concentration-time profile show?
Input controlled No absorption Disposition only - Distribution - Metabolism - Excretion
What does an intermittent IV infusion concentration-time profile show?
Input controlled No absorption Disposition only - Distribution - Metabolism - Excretion
What does an extravascular single dose concentration-time profile show?
Absorption Disposition - Distribution - Metabolism - Excretion
sharp Increase in plasma concentration then steady decrease as it gets elimniated
What does an extravascular multiple dose concentration-time profile show?
Absorption Disposition - Distribution - Metabolism - Excretion
fluctuation in plasma concentration but gradually increasing until steady state
What is achieved after 5 doses of medication?
Steady state
may vary depending on half lives and rate of absorbtion
What is the principle of therapeutic drug monitoring?
Therapeutic and toxic effects related to concentration
Knowledge of measured drug levels can influence management
Why is Therapeutic Drug Monitoring important?
Concentration related effects of drug either of lack of efficacy or toxicity are not easily assessed, identified or differentiated early enough by clinical signs alone
Concerns on patient adherence
- are they going to keep taking it
Inter-individual PK variability associated with narrow therapeutic window
