L40 - Intro to Pharmacokinetics

• Define dose


  predetermined amount of the drug administered at one time to produce a certain degree of biological response. Eg 200mg.
• Define dosage


  Predetermined amount and rate of administration of a drug.

  
  

  Eg 200mg od.
• Define dosage form.


  Physical form in which a precise mixture of API and excipients are presented to aid administration, delivery to site of action and improve bioavailability.

  
  

  Eg 200mg tablet.
• Define dosage regimen.


  The schedule of doses of a therapeutic agent per unit time.
• What does dosage regimen include?

  - Time between doses.

  
  

  - Time when doses are to be given.

  
  

  - Amount of medicine to be given per unit time.
• How can we establish a dosage regimen?

  - Dose, interval between doses and route of administration monitored.

  
  

  - Regimes changes empirically until response sufficient.

  
  

  - Needs large no. of pts and experimentation.

  
  

  - Assumption: Cp = [drug] at target site.

  
• What factors do we need to consider when establishing a dosage regime?

  - Potency.

  
  

  - MEC/MTC and therapeutic window.

  
  

  - Oral admin./bioavailability.

  
  

  - IV infusion: how fast?

  
  

  - Time and extent of distribution to target.

  
  

  - How quickly drug is eliminated.

  
  

  - Elderly/paediatric/pregnant pts.

  
  

  - Renal/hepatic insufficiency.

  
• Define pharmacokinetics in terms of foriegn chemicals.

  Pharmacokinetics = movement of foriegn chemicals (xenobiotics) during their passage through the body.

  
  

  
  

  What the body does to the drug!
• What does the pharmacokinetic phase describe?

  - Relationship between drug input (determined by dosage regimen) and [drug] achieved with time.

  
  

  - The science of kinetics of drug absorption, distribution and elimination.

  
• Define biopharmaceutics


  The study of the interrelationships between drug physicochemical properties, dosage form and administration route with rate and extent of absorption and disposition of the drug.

  
• How do we find disposition of a drug?

  Disposition = Distribution + Elimination
• What is the therapeutic window?

  The range of concentrations between MEC and MTC associated with therapeutic success.

  
• What is a pharmacokinetic model?


  A set of mathematical expressions that quantitatively describe ADME processes and their relationships.
• How can we use pharmacokinetic models?

  - To describe complexity of ADME.

  
  

  - Predict [drug] in plasma, tissue, urine so efficacy/toxicity.

  
  

  - Estimate drug/metabolite accumulation.

  
  

  - Establish dosing regimes.

  
  

  - Measure/compare rate and extent of absorption, hence bioavailability and bioequivalence.

  
  

  - Describe and predict variability in drug therapy.

  
  

  - Predict and explain drug interactions.
• What is the aim of a pharmacokinetic model?

  To predict the Cp of a drug and its metabolites at a given time after administration.
• What are the independent and dependent variables in PK models?

  Independent = time.

  
  

  Dependent = [drug] in plasma/urine/tissue etc.

  
• What are PK parameters used in PK models?

  - Volume of Distribution.

  
  

  - Clearance.

  
  

  - Elimination rate constant, k.

  
  

  - Half-life, t1/2.

  
  

  - Absorption rate constant, ka.(Formulation dependent).

  
  

  - Fraction absorbed. (Formulation dependent)

  
• What is compartmental modelling?

  Compartment = body volume comprising a group of tissues/fluids which have similar properties (eg blood flow/drug affinity).

  
  

  - A drug is evenly distributed in a compartment.