2. Video 1 – Drug
Administration
LAS20061 – Lecture 5
Pharmacokinetics 1 – Drug Absorption and
Distribution
3.
4. Routes of Administration
Enteral – via the GI tract (mouth
to rectum) to increase blood levels
Parenteral – avoiding the GI tract
to increase blood levels
Topical – at the site where the
drug is needed (avoiding increased
blood levels)
6. • High drug concentration
in portal vein cf
peripheral circulation
• High rate of enzyme
activity (because of
Michaelis Menten
kinetics)
• Large proportion of drug
removed from hepatic
circulation
7. Enteral
Administration
Oral
Buccal,
Lingual
Rectal
Convenient & cheap
Absorption along whole GI Tract
Hurdles to absorption
First pass metabolism
Effects on GI
N&V, emergency situations
First pass
avoided
Rapid absorption
Low surface area
for absorption
Mouth-
experience
Small doses
First-pass
reduced
Rapid absorption
Absorption
erratic
Compliance
11. Inhalation
ADVANTAGES
LOCAL DELIVERY
HIGHER
CONCENTRATIONS IN
TARGET ORGAN
AVOID SYSTEMIC
Adverse Drug Responses
NO FIRST PASS
METABOLISM
DISADVANTAGES
DELIVERY CUMBERSOME
AND TIME CONSUMING
COMPLIANCE
DELIVERY SYSTEMS
COSTLY
LOCAL IRRITATION RISK
HARD TO USE IN
RESPIRATORY EMERGENCY
12.
13. Video 2 – Drug
Absorption
LAS20061 – Lecture 5
Pharmacokinetics 1 – Drug Absorption and
Distribution
14.
15. There are four main ways by which a small molecule can
cross a cell membrane:
A. Diffusion through the
lipid bilayer
B. Passive transport via
transporter proteins
C. Active transport via
pumps or co-
transporters
D. Vesicular transport
(pinocytosis, endo- and
exo-cytosis)
A. Diffusion through the
lipid bilayer
16. Extracellular Compartment Intracellular Compartment
Drugs diffuse from high concentration to low
• High extracellular concentrations drive absorption
• Drug solubility determines drug concentration available for absorption in GI tract
Cell
Membrane
19. Extracellular Compartment Intracellular Compartment
Lipophilicity and Absorption
• Lipophilicity determines a drug’s propensity to diffuse from the gut lumen into the cell
membrane…
• …and from the membrane into the cell cytoplasm
Cell
Membrane
20. Lipophilicity measured by LogP
Concentration
in octanol
Concentration
in water
LogP=log
[Drug]octanol
[Drug]water
LogP>0, [Drug]octanol > [Drug]water - lipophilic
LogP<0, [Drug]water > [Drug]octanol - hydrophilic
21. Lipophilicity affects rate of absorption
Drugs that are not rapidly
absorbed will be metabolised
and excreted before
intracellular concentrations
reach desired levels
25. • pH changes throughout the
intestine
• Drugs with different pKa will
be ionised to different
extents at different parts of
the intestine
• Absorption will be greatedt
when ionisation is lowest
• pKa will affect degree to
which drugs are absorbed
Gut pH affects ionisation and rate of absorption
26.
27.
28. Video 3 – Drug
Distribution
LAS20061 – Lecture 5
Pharmacokinetics 1 – Drug Absorption and
Distribution
29.
30.
31.
32. Enable active pumping
of drugs out of brain Rich in metabolic enzymes –
destroy drugs entering the brain
33.
34.
35.
36. logP = 1.52
Octanol:water = 38.0
logP = 0.43
Octanol:water = 7.4
Assuming same brain:plasma ratios, this allows >5-fold lower blood concentrations for the same
brain concentration. This reduces overall dose, and side effect risk – or alternatively, for the
same dose induces greater “recreational” effects.
In fact, Heroin is only ~2x more potent – other factors are also important
Case Study: Morphine and Heroin
