bioavailability & first-pass

What is bioavailability?

The fraction of active form of a drug that reaches the plasma

What percent bioavailability do intravenous (IV) administrated drugs have?

100%

• because the drug is delivered directly to the bloodstream

For oral drugs, bioavailability is usually (less than/equal to) 100%?

LESS THAN!

• incomplete absorption

• First-pass metabolism in the liver (drug is partially broken down before reaching systemic regulation)

True or False: Bioavailability determines the dosage of a particular drug….so a drug with a low oral bioavailability may need a higher dose or a different route

TRUE

Which factor would increase the oral bioavailability of a drug?

A. High first-pass metabolism

B. Poor water solubility

C. Delayed gastric emptying

D. Enteric coating that protects the drug from stomach acid

D. Enteric coating that protects the drug from stomach acid

What is the first-pass effect?

Refers to the initial metabolism of a drug in the liver (and sometimes the gut wall) after it is absorbed from the gastrointestinal tract, but before it reaches systemic circulation

• this process reduces the concentration of the active drig that ultimately enters the bloodstream

What is the order of events in the first-pass effect?

A drug is taken orally and absorbed into the small intestine → it enters the portal vein, which carries blood directly to the liver → in the liver, enzymes (like cytochrome P450) metabolize part of the drug → the remaining unchanged drug enters systemic regulation

Drugs with a high first-pass effect may require what kind of modifications?

• higher oral doses

• Alternative administration routes (sublingual, rectal, IV)

What are the 5 drug administration routes that bypass the first-pass effect?

1- intravenous (IV)

2- sublingual

3- rectal (partially)

4- transdermal

5- inhalation