Posted by Cam W. on May 8, 2002, at 0:58:09
In reply to WARNING: hardcore technical moclobemide question, posted by Will_Hung on May 7, 2002, at 17:12:21
Will - First pass effect was at one time thought to mainly involve the liver and the cytochrome P450 enzymes contained within. Now first pass effect is thought to involve the cytochrome P450 enzymes at the interface between between the intestines and the surrounding blood vessel. I have done some research of this phenomenon with Zoloft™ (sertraline).
There is an abundance of cytochrome enzymes within the cells of the of the intestine where absorption of medication is taking place. It is this "first pass" that is substantialy reducing the amount of intact parent drug reaching the interior of the body.
There is a way to minimize this metabolism within the walls of the intestine. One must increase the blood flow through the blood vessels surrounding the intestine. This can be acheived by taking the drug with a meal. The presence of food in the intestine increases the blood flow through these instestinal blood vessels, as the body prepares itself to absorb the food. This increased blood flow allows more of the intact drug to enter the body, as the cytochrome enzymes cannot keep up with the drug's quicker absorption. Also, the presence of food and the increase in local blood circulation play a major role in decreasing the efficiency of the cytochrome enzymes in metabolizing the drug.
This does not work for all drugs, especially those that either are not metabolized solely by the cytochrome system (ie. metabolism within the bloodstream) or are not metabolized by the cytochrome system to a very small extent or are excreted from the body without being metbolized.
Other drugs (especially those that are polar molecules) can be mechanically trapped by certain foodstuffs, and sent through the intestines and out through the feces without ever entering the body. This reduces the medicinal effect of the drug by a greater degree than the first pass effect ever could.
When it comes to the pharmacology of drugs, things are never as simple as they first seem. - Cam
poster:Cam W.
thread:105468
URL: http://www.dr-bob.org/babble/20020503/msgs/105534.html