1. Tutorial 1
January 18, 2013

2. Contact Details Two TAs
Julian Chesterman Biosciences 1424
Cody Brown
HMRC 5-201

3. Quick Overview of Course to Date
Definition of drug/objectives of drug dosage formulation
Drug - substance or mixture of substances advertised for treatment or prevention of disease or symptoms, e.g. Aspirin
Drug dosage – include excipients to facilitate/control delivery of drug, protect drug from degradation, conceal taste/odor
Want predictable and repeatable therapeutic response

4. Plasma Concentration (Cp)
Key Definitions
Bioavailability: extent of absorption and the rate at which an administered dose reaches systemic circulation in its active form
Therapeutic Window:
Time after Administration
Plasma Concentration (Cp)
Minimum Effective Concentration
Minimum Toxic Concentration

5. Hepatic First Pass Effect
Everything absorbed in the intestines enters the portal vein and is transported directly to the liver
Liver (poison filter) is responsible for metabolizing chemicals in the blood
Consequently a portion of the drug will be metabolized before it ever reaches systemic circulation

6. Routes of Administration –Pros/Cons
Oral
Pro: Patient Compliance
Con: Hepatic first-pass effect/Too slow for emergencies
Rectal
Pro: Avoids some hepatic first-pass effect
Con: Low buffering capacity of fluid

7. Routes of Administration –Pros/Cons
Buccal/Sublingual
Pro: Rapid absorption/no first-pass effect
Con: Bad taste of drugs/small doses
Parenteral (Intravenous/Subcutaneous, etc.)
Pro: 100% available/rapid delivery (emergencies)
Con: Patient compliance (fear of needles/need for training)

8. Routes of Administration –Pros/Cons
Transdermal
Pro: Convenient/sustained release (good for drugs with narrow therapeutic window or requiring frequent delivery by other methods)
Con: Drug must be potent and effective when delivered slowly
Nasal
Pro: bioavailability similar to injection for some drugs
Con: Formulation complexity/shelf-life

9. Routes of Administration –Pros/Cons
Pulmonary
Pro: Large surface area and thin membrane
Con: More complex to formulate

10. Drug Absorption Simple diffusion
Because viscosity of the phospholipid bilayer is 100 to 1000 times higher than that of water, movement across cell membranes (hydrophobic region) is the rate-limiting step in drug absorption by simple diffusion (Stokes-Einstein equation).
Not all molecules can diffuse across
phospholipid bilayer.

11. Drug Absorption Facilitated Diffusion:
Transport across cell membrane via carrier proteins. Transport from high concentration to low concentration.
Active Transport:
Transport across cell membrane against a concentration gradient . Requires expenditure of energy by cell.