BIO200 Bioavailability

PO

• oral or by mouth

• never reach 100% bioavailability

• most convenient

• first pass effect might be important

IV

• Intravenous

• 100% bioavailability

• most rapid onset

IM

• Intramuscular

• released over time to the blood vessels of the muscle

• for nonpolar drug

• can get close to 100 bioavailability

• large volumes often feasible

• may be painful

Sub cut

• Subcutaneous under the skin in the fat depot then release to blood

• good for delayed release, but difficult for many patients due to restricted mobility/ pain

• Some drugs are too nonpolar to go into the blood and need to go intramuscular

• bioavailability is usually less than 100%, but can get close

• smaller volume than IM, may be painful

PR

• per rectum

• the lower part of the rectum goes right to the systematic veins, leading to rapid distribution (not on the same level as IV) and skip the first pass metabolism

• the upper part goes to the portal vein → go through first pass metabolism → good thing if administer prodrug

• less first pass effect than oral

Inhalation

• from lungs to blood stream → 100% to lung tissue

• often very rapid onset

Topical

• to skin, nose, eye

• act locally

Transdermal

• nicotine patch

• absorb to blood stream, not treat the skin

• usually very slow

• used for lack of first pass effect

• prolong duration of action

Intranasal

to the blood stream to the pituitary gland

→ so not local?

Intrathecal

• to the csf to bypass the BBB

epidural

• outside dura matter

intra-articular

• inside joint space

First pass effect

metabolism where the drug will be turned into another compound, either inactivate or activate it

First pass elimination

initial metabolism by the liver through the portal vein

Examples of factors affecting bioavailability:

• Extent of Absorption across gut wall (ex./ too hydrophobic or too hydrophilic drugs = incomplete absorption, low bioavailability;

• Grapefruit juice enhances bioavailability! inhibit P-glycoprotein : P-glycoprotein actively pump drugs back to gut lumen

• Grapefruit juice enhances bioavailability! inhibitor of the intestinal cytochrome P-450 3A4 system, which is responsible for the first-pass metabolism of many medications.

• First-Pass Elimination (initial metabolism of drug by liver)

first pass effect in PO

• as drug absorb through gut wall into capillaries, blood flows through hepatic portal vein into the liver

• the liver metabolise drug prior to reaching systematic circulation

→ can excrete drug into bile

→ drugs can also be metabolised in the gut wall

Area under the curve (AUC)

total drug exposure over time;

correlates to total absorption and

it is proportional to the dose and

extent of bioavailability