The Liver Filter: First-Pass and Pro-drug Activation Quiz

Orally administered drugs are absorbed in the GI tract and carried via the portal vein directly to the liver. This allows the liver to metabolize the drug before it ever reaches the general circulation.

A high extraction ratio means the liver removes most of the drug from the blood on its first pass. This results in a low fraction of the dose reaching the systemic circulation.

Esterases are ubiquitous enzymes that hydrolyze the ester bond of a pro drug to release the active carboxylic acid form which is often more polar and active.

By temporarily attaching a promoiety chemists can alter the physical properties of a drug to improve patient compliance or absorption without changing the active scaffold permanently.

Bioprecursors do not have a specific carrier group. Instead the entire molecule undergoes a chemical change catalyzed by enzymes to reach its active form.

Drugs absorbed under the tongue enter the systemic venous drainage directly. This avoids the portal vein and prevents the liver from metabolizing the drug immediately after absorption.

Sulfasalazine contains an azo bond that is cleaved by bacteria in the large intestine. This releases the active anti inflammatory drug exactly where it is needed.

All of these compounds are pharmacologically inactive or significantly less active until they are metabolized by specific enzymes in the body.

The promoiety is the carrier part that is cleaved off by the body to reveal the active drug molecule after the desired absorption has occurred.

By masking an acidic or reactive functional group as an ester or amide the pro drug can pass through the stomach without causing local damage before being activated in the blood or liver.

DOPA decarboxylase removes a carboxyl group from the Levodopa molecule to create the active neurotransmitter Dopamine which can then act in the brain.

Anything that affects enzyme activity or the rate at which the drug is delivered to the liver will change how much of the drug survives the first pass.

An extraction ratio of zero means the concentration of the drug is the same entering and leaving the liver indicating no first pass removal occurred.

Valacyclovir is an amino acid ester of Acyclovir. It uses intestinal transporters to achieve much higher blood levels than Acyclovir alone could achieve.

Cyclophosphamide is oxidized by P450 enzymes in the liver to form a metabolite that eventually breaks down into the active DNA alkylating agent.