Drug Metabolism Overview & Purpose

drug metabolism

the biochemical changes that occur on drug molecules or other foreign compounds, the purpose of which is to facilitate elimination

-drug (lipophilic) —enzyme→ metabolite (polar) → excretion

site of drug biotransformation

liver (most drug metabolizing enzymes)

-first pass effect → lower bioavailability

-also intestine, kidneys, lungs, skin, placenta, brain, adrenal glands

phase I reactions

oxidation, reduction, hydrolysis

-introduces polar functional groups

phase II reactions

conjugation (glucuronic acid, sulfate, amino acid conjugation) increase solubility

-other conjugation (methylation, acetylation, glutathione conjugation) lower solubility

-attaches polar & ionizable endogenous groups so as to achieve a more complete solubility

-lowers biological activity

oxidative biotransformations of drugs

most widespread, most important

enzyme system

most important CYP-450 (transfers oxygen atom to R-H)

COVID

causes significant inflammatory response in all patients; inflammation decreases the activity of most CYP450 enzymes

COVID pathway

COVID enters into body → extreme increase of inflammatory cytokines → hyperinflammatory/cytokine syndrome → inflamed liver → suppression of hepatic CYP450 enzymes → decreased drug metabolism & lower drug clearance → higher plasma drug concentration & severe toxicity → deterioration of COVID patient’s condition

-lesser response if drug is prodrug

Paxlovid

for COVID treatment; can be prescribed by pharmacists

-mechanism of action includes ritonavir → slow down metabolism of Nirmatrelvir

pharmacokinetic enhancers (boosters)

used to increase the effectiveness of another drug by inhibiting metabolism & reducing drug clearance (ex. Norvir, Tybost)