Metabolism and elimination of drugs

First Pass Effect

● Oral meds only!

● Absorbed from gut, then enter hepatic portal circulation where blood is filter by the liver before entering systemic circulation

● Some of drug may be metabolized before it reaches systemic circulation and target site

● For some drugs this decreases bioavailability to amounts so low it is ineffective ○ Oral diazepam - 3%

Elimination: Renal

● Major route for excretion

● Water soluble - often happens through metabolism

● Kidneys must be healthy

● Normal renal blood flow

● Lower urinary tract must be functioning

Elimination: Biliary excretion

● Liver excretes drugs into bile (high lipid-soluble drugs)

● Bile secreted into GIT

● Drug eliminated through feces or enters enterohepatic cycle

Elimination: Intestinal Excretion

● Secreted across the GIT mucosa by active transport

● Can also be excreted in gut secretions (ruminant saliva)

● Ruminants produce alkaline saliva which traps acidic drugs and metabolites

● Eliminated in the feces

Elimination: Glandular Secretions

● Salivary, mammary , and sweat glands

● MILK!! - affect offspring or humans

● Drug found in meat or milk - residues

● Potentially dangerous - allergic reactions, resistant bacteria

Elimination: Lungs

Gas anesthetics eliminated in expired air

Elimination: Half-life

Time required for the blood concentration of a drug to decrease/eliminated by 50%

● Useful to determine dosing intervals

● Takes approximately ten half-lives (T1/2s) to eliminate 99.9% of a drug from the plasma

● Does not mean that all the drug is gone from body!