Factors That Affect Drug Metabolism
The duration and intensity of pharmacological action of most lipophilic drugs are determined by the rate they are metabolized to inactive products. The Cytochrome P450 monooxygenase system is the most important pathway in this regard. In general, anything that increases the rate of metabolism (e.g., enzyme induction) of a pharmacologically active metabolite will decrease the duration and intensity of the drug action. The opposite is also true (e.g., enzyme inhibition). However, in cases where an enzyme is responsible for metabolizing a pro-drug into a drug, enzyme induction can speed up this conversion and increase drug levels, potentially causing toxicity.
Various physiological and pathological factors can also affect drug metabolism. Physiological factors that can influence drug metabolism include age, individual variation (e.g., pharmacogenetics), enterohepatic circulation, nutrition, intestinal flora, or sex differences.
In general, drugs are metabolized more slowly in fetal, neonatal and elderly humans and animals than in adults.
Genetic variation (polymorphism) accounts for some of the variability in the effect of drugs. With N-acetyltransferases (involved in Phase II reactions), individual variation creates a group of people who acetylate slowly (slow acetylators) and those who acetylate quickly, split roughly 50:50 in the population of Canada. This variation may have dramatic consequences, as the slow acetylators are more prone to dose-dependent toxicity.
Cytochrome P450 monooxygenase system enzymes can also vary across individuals, with deficiencies occurring in 1 - 30% of people, depending on their ethnic background.
Pathological factors can also influence drug metabolism, including liver, kidney, or heart diseases.
In silico modelling and simulation methods allow drug metabolism to be predicted in virtual patient populations prior to performing clinical studies in human subjects. This can be used to identify individuals most at risk from adverse reaction.
Read more about this topic: Drug Metabolism
Famous quotes containing the words factors that, factors, affect, drug and/or metabolism:
“Language makes it possible for a child to incorporate his parents’ verbal prohibitions, to make them part of himself....We don’t speak of a conscience yet in the child who is just acquiring language, but we can see very clearly how language plays an indispensable role in the formation of conscience. In fact, the moral achievement of man, the whole complex of factors that go into the organization of conscience is very largely based upon language.”
—Selma H. Fraiberg (20th century)
“I always knew I wanted to be somebody. I think that’s where it begins. People decide, “I want to be somebody. I want to make a contribution. I want to leave my mark here.” Then different factors contribute to how you will do that.”
—Faith Ringgold (b. 1934)
“The world-spirit is a good swimmer, and storms and waves can not drown him. He snaps his fingers at laws; and so, throughout history, heaven seems to affect low and poor means. Through the years and the centuries, through evil agents, through toys and atoms, a great and beneficent tendency irresistibly streams.”
—Ralph Waldo Emerson (1803–1882)
“He’d been numb a long time, years. All his nights down Ninsei, his nights with Linda, numb in bed and numb at the cold sweating center of every drug deal. But now he’d found this warm thing, this chip of murder. Meat, some part of him said. It’s the meat talking, ignore it.”
—William Gibson (b. 1948)
“He’s got a fifteen percent metabolism with an overactive thyroid and a glandular affectation of about three percent. With a one percent mentality. He’s what we designate as the Crummy Moronic type.”
—Robert Pirosh, U.S. screenwriter, George Seaton, George Oppenheimer, and Sam Wood. Dr. Hugo Z. Hackenbush (Groucho Marx)