Absorption and Distribution

What are the major routes of drug administration?

gastrointestinal, lungs, skin, intravenous, intramuscular

What is the drug administration site for GI absorption route?

oral

What is the drug administration site for pulmonary absorption route?

inhalation

What is the drug administration site for intravenous absorption route?

directly into blood stream via vein

What is the drug administration site for intramuscular absorption route?

directly into muscle

What factors affect drug absorption in the GI tract?

physical chemical properties (e.g., Lipinki’s Rule of 5), drug stability, complexation, gastric-emptying time, blood flow, pathological factors, drug pharmaceutical properties, surface area of GI tract, density of protein transporters, first-pass effects

How do the physical chemical properties of a drug affect absorption in the GI tract?

Lipinki’s Rule of 5!

• MW < 500

• Lipophilicity < 5

• Substance has < 5 H-bond donor groups (i.e., NH and OH)

• Substance has < 10 H-bond acceptor groups (i.e., N and O)

How does stability of a drug affect absorption in the GI tract?

Some drugs cannot be absorbed until they are enzymatically degraded while others can’t be absorbed because they are enzymatically degraded

Some drugs have an enteric compound to protect them from degradation via stomach acid

How does complexation affect absorption in the GI tract?

drug forms complex(es) with other compound which may make them too large for passive diffusion

How do pharmaceutical properties of a drug affect absorption in the GI tract?

some drugs have special coatings or ingredients that control drug release (i.e., extended release drugs)

drugs have varying disintegration and dissolution

Drug disintegration

process of breaking into pieces

Drug dissolution

drug dissolves to free drug

How does surface area affect absorption in the GI tract?

increases absorption

What contributes to increased SA in the GI?

small intestine epithelial villi and microvilli

What contributes to increased SA in the lung?

alveoli

What is Lipinki’s Rule of 5?

rules that can be used to determine if a drug is likely to be absorbed

rules include the following:

• MW < 500

• Lipophilicity < 5

• Substance has < 5 H-bond donor groups (i.e., NH and OH)

• Substance has < 10 H-bond acceptor groups (i.e., N and O)

What factors affect drug absorption in the lung?

surface area, thin diffusion distance across alveolar wall, blood flow, lipophilicity, solubility, particle size

What factors affect drug absorption in the skin?

surface area, method of drug administration (i.e., topical, dermal, epidermal, percutaneous)

Passive transport

transport of solute across the plasma membrane without the use of a protein helper

Active transport

transport of solute across the plasma membrane with ATP

Bioavailability

area under curve of any route / area under curve of IV administration

Distribution

movement of chemicals away from the site of absorption to the ECF and cells

Plasma protein binding

largely reversible binding of a chemical to blood plasma proteins

What are some characteristics of plasma protein binding?

reversible

saturable

competitive

How does plasma protein binding affect distribution?

decreases concentration of free drug and therefore decreases distribution

How does plasma protein binding affect absorption?

may increase absorption into the blood

Examples of plasma proteins

albumin, lipoproteins, metal-binding proteins