Principles of Pharmacokinetics 𝑇1/2 = (0.

7 𝑥 𝑉)/𝐶𝐿
There are 4 half lives before administering drug
Dynamics of drug absorption, distribution and elimination Steady state- concentration builds up

 Absorption
 Distribution Why is it important to know the half life of the drug?
 Metabolism
 Excretion - The therapeutic levels of a drug can be obtained
more rapidly by delivering a loading dose
Pharmacokinetics followed by maintenance doses

- Pro drug Loading dose

- Inactive precursor chemical that is readily
absorbed and distributed and converted to active - An initial dose of a drug that is higher than
drug by biologic processes subsequent doses to achieve the therapeutic
drug concentrations in the serum rapidly
Permeation
Maintaining dose
- Process in which drug is absorbed into the blood
from its site of administration and distributed to - Doses of drug that maintain a steady plasma
site of action concentration in the therapeutic range

Kinds of permeation: Onset

 Aqueous diffusion- occurs within the larger - Amount of time it takes a drug to begin working
aqueous compartments of the body and across
Duration
epithelial membrane tight junctions and
endothelial lining of the blood vessels through - The length of time for which a drug is therapeutic
aqueous pores; 20,000-30,000 MW;
concentration gradient: Fick’s law Bioavailability
 Lipid diffusion- most important limiting factor
for drug permeation - The fraction of unchanged drug reaching the
 Special carriers- by active transport and systemic circulation following administration by
facilitated diffusion that are selective, saturate any route
and inhibitable
Routes of administration:
 Endocytosis and exocytosis- bound at cell
surface receptor (e.g Vitamin B12- upper  Intravenous- best way; 100 bioavailability
jejunum and duodenum, iron- ileum)  Intramuscular- 75-≤100
 Subcutaneous- 75-≤ 100
Pharmacokinetic parameters
 Per oral- 5- <100
 Clearance- the measure of the ability of the  Per rectal- 30- <100
body to eliminate the drug; mg/L or mg/hr (e.g  Inhalation- 5-100
liver, kidney lungs)  Transdermal- 80-100
 Volume of distribution- the measure of the  Sublingual
apparent space in the body available to contain  Topical
the drug
𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 Intravenous
𝑉𝑑 =
𝑐𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒
<7= plasma - Most rapid
7-15= blood - Useful in emergencies and in unconscious
>42= tissues patients
- Insoluble drugs cannot be administered through
 Half life- the amount of time required for the
intravenous
plasma concentration of a drug to decrease by
50%

Lyca A.
Intramuscular - Dermatologic and ophthalmologic preparations

- Drug passes through capillary walls to enter the

blood stream
- Rate of absorption depends on the formulation 1. Extent of absorption
- Large volume
- Lack of absorption from gut
Subcutaneous - Hydrophilic- not permeable to non polar/ lipid
cell membrane
- Drug is injected beneath the skin and permeates - Lipophilic- not permeable to water cell
capillary walls to enter the blood stream membrane
- Small volume
2. Rate of absorption
Oral
- The rate of absorption is determined by the site
- Most compatible with drugs that are self of administration and the drug formulation
administered
- Must withstand the acidic environment of the Bioavailability is affect by extent and rate of
stomach absorption
- Must permeate the gut lining before entering the
blood stream
- First pass Gut wall= CYP3A4
- Most convenient
↓
Rectal
Portal circulation
- Useful for unconscious or vomiting patients or
small children ↓
- Absorption is unreliable
- Less first pass effect Liver= CYP450 cytochrome oxidase

Inhalation ↓

- Metered doses Systemic circulation

- Suitable for self administration
First pass elimination
- Rapid onset

Transdermal
First pass effect
- “Patch”- skin and capillary bed
- Convenient for self administration - Phenomenon that greatly reduced effect before
- Long duration the drug reach the systemic circulation
- Lack first pass effect
- Slow absorption Time course of drug effects

Sublingual  Immediate
 Delayed
- Good absorption
 Cumulative
- Easily administered drugs
- Because the stomach is bypassed, acid-lability
and gut-permeability need not be considered

Topical

- Useful for local delivery of agents, particularly

those which have toxic effects if administered
systematically
Lyca A.