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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by Will_Hung on May 7, 2002, at 17:12:21
I'm currently taking 750mg/day in the form of 2x375mg divided dose with about 1.5 - 2 hours in between doses. Thing is, I want to get the maximum possible effect from this drug as I cant take the dose any higher and its served me quite well so far.
Anyway, I've read about something called the "first-pass effect" which apparently removes about 50% of a single dose of the drug from the body via the liver before it reaches the bloodstream. Multiple dosing means that about 85% of the the dose reaches the bloodstream. My question is this: if I am taking the drug divided over only a 2-hour period will my liver treat each days Moclobemide as a 'single dose' and remove 50% of it before it gets into my bloodstream? After all, the other 22-hours in between equals about 10 half-lives for moclobemide. In other words am I currently wasting half of my AD by not dividing the drug over a longer period of time (say 5-6 hours)?
Also, are side effects be affected by dividing the dose over a longer period of time?I hope that I have got my question(s) across well because as you can see its sort of complicated. I have looked for information on this on the internet but all I have found so far are university lecture notes on the liver!
Cheers
Will
Posted by djmmm on May 7, 2002, at 19:12:50
In reply to WARNING: hardcore technical moclobemide question, posted by Will_Hung on May 7, 2002, at 17:12:21
At 750mg, the concentrations tend to go up and the half-life increases too. The half life is about 2 hours for the minimum dose.
the pharmacokinetics of a MAOI are a bit different than typical Antidepressants, because MAOI activity isn't necessarily correlated with half-life..in other words, MAO-A inhibition lasts much longer than the half-life of the actual drug, (probably about 20 or more hours)
Posted by katekite on May 7, 2002, at 20:07:49
In reply to WARNING: hardcore technical moclobemide question, posted by Will_Hung on May 7, 2002, at 17:12:21
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
Posted by Will_Hung on May 8, 2002, at 18:10:18
In reply to Re: WARNING: hardcore technical moclobemide question » Will_Hung, posted by Cam W. on May 8, 2002, at 0:58:09
Cam,
I enjoyed reading your informative and well-written response. Something is bothering me, however. In the moclobemide data sheet it says, and I quote, "the presence of food reduces the rate, but not the extent of moclobemide absorption". This would seeem to contradict your explaination. Am I missing something here?
Secondly, do you have any thoughts on whether I would gain anything from dividing the doses further apart? My current thinking is this: multiple dosing reduces the hepatic first-pass effect, presumably because over time it supresses the P450 enzymes in the intestines. However, If I take my doses only 2 hours apart, then I am leaving another 22 hours for my little cytochromic buddies to regenerate. In other words, the first-pass effect is greater than it would be if I spread the doses out. Hmmmmmmmmmmmmm... Just a thought.Thanks in advance,
Will HP.S. Im starting a degree course in Pharmacology in September. No really.
Posted by jane d on May 13, 2002, at 17:07:48
In reply to Re: WARNING: hardcore technical moclobemide question » Will_Hung, posted by Cam W. on May 8, 2002, at 0:58:09
I thought Cam's explanation further up in the thread of how food and drugs interacted was great. I'm now wondering about my coffee. Does it interact with those "empty stomach" meds? If it's with milk? With sugar? Is swallowing those pills with a mouthful of pepsi a no no? The explanation above makes me think the answer is probably "it depends" but, in that case, does anyone have any suggestions on how to find this out for specific drugs?
Jane
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