Superfluous
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- Mar 16, 2019
- 973
I was initially going to post this when I was ready to start the regimen. However, as I have been allowed some time to consider my options, I've decided to post it beforehand to give others an opportunity to review and comment on it, and maybe even help to improve it.
Disclaimer: I am not a medical professional, and I will/may be conducting this trial purely based on my own investigations. I am neither proposing nor recommending this as a reliable regimen.
This 'ahead' regimen differs somewhat from any of the recommended ahead regimens described in any of the literature currently available (Five Last Acts, PPeH March 2019, Wikibooks).
The purpose of this regimen is to achieve higher plasma concentrations of domperidone in the body without introducing risk.
The reason why I have chosen to try a slightly different regimen is that most of the current literature focuses on metoclopramide as the anti-emetic of choice, and domperidone is known to be weaker. I feel, therefore, that it's more important to try and achieve higher plasma concentrations of domperidone to provide the same or similar success levels when it comes to reducing the risk of vomiting. I am, of course, assuming that higher plasma concentrations will reduce the risk of vomiting.
It's broken up into sections to make it easier to read.
Please feel free to comment. Any and all thoughts or ideas are welcome, and any links to other similar studies would be very useful.
If I receive more data (or can find more myself) that could improve this regimen, then I will incorporate it and create a new post if/when I plan to start.
If I receive data that would invalidate this regimen, then I will obviously not attempt to use it and will request that the thread be deleted.
Otherwise, if/when the time comes, then I will resurrect this thread and provide feedback on progress and success/failure as is appropriate.
Disclaimer: I am not a medical professional, and I will/may be conducting this trial purely based on my own investigations. I am neither proposing nor recommending this as a reliable regimen.
This 'ahead' regimen differs somewhat from any of the recommended ahead regimens described in any of the literature currently available (Five Last Acts, PPeH March 2019, Wikibooks).
The purpose of this regimen is to achieve higher plasma concentrations of domperidone in the body without introducing risk.
The reason why I have chosen to try a slightly different regimen is that most of the current literature focuses on metoclopramide as the anti-emetic of choice, and domperidone is known to be weaker. I feel, therefore, that it's more important to try and achieve higher plasma concentrations of domperidone to provide the same or similar success levels when it comes to reducing the risk of vomiting. I am, of course, assuming that higher plasma concentrations will reduce the risk of vomiting.
It's broken up into sections to make it easier to read.
I have found what I consider to be a reliable study published on eMC (electronic Medicines Compendium) that provides some detailed information on domperidone plasma concentration levels. You can check the link as to who they are if you like.
The specific study is this:
You don't need to read through the complete article as I will be referencing the appropriate sections as I go, but feel free to do so if you prefer.
The specific study is this:
Domperidone 10mg Tablets - Summary of Product Characteristics (SmPC) - (emc)
Domperidone 10mg Tablets - Summary of Product Characteristics (SmPC) by Aurobindo Pharma - Milpharm Ltd.
www.medicines.org.uk
You don't need to read through the complete article as I will be referencing the appropriate sections as I go, but feel free to do so if you prefer.
The primary purpose of the study was to prove the safety of domperidone as a treatment for various conditions, nausea included, specifically in relation to the risks of QT prolongation. In doing so, it also monitored concentration levels of domperidone in blood plasma, and it's this specific data I am using. It also 'proves' (and I use this term loosely) the lack of risk of QT prolongation with the dosages used in the trials.
There are no specific values relating to plasma concentrations in either the study or my post. Also, I have no comparative data between the effectiveness of metoclopramide over domperidone for the purpose of reducing the risk of vomiting. All references to plasma concentrations of domperidone are relative.
This is always a difficult question to answer. I've read and have copies of Bad Pharma and Bad Medicine, both written by Ben Goldacre MBE, so I have a basic grasp of how to identify good studies from bad. However, I am not an expert.
In my opinion, the first indication that's it's a good study is the level of detail included.
Next, it is recent (or was at least recently updated on 14th June 2019 last time I checked).
In section 4.8 Undesirable effects, it outlines the details of the trials.
On the positive side, the 31 trials were all double-blind and placebo-controlled, which is good. 1275 patients isn't a lot, but it's better than some. It also covers a wide range of conditions.
On the negative side, it was conducted by a pharmaceutical company testing their own product.
As the median duration of the 31 trials was 28 days and the maximum trial length was 28 days, we can deduce that at least 16 of the trials had a duration of 28 days.
No such deduction can be made regarding daily dosages.
In my opinion, the first indication that's it's a good study is the level of detail included.
Next, it is recent (or was at least recently updated on 14th June 2019 last time I checked).
In section 4.8 Undesirable effects, it outlines the details of the trials.
The safety of domperidone was evaluated in clinical trials and in postmarketing experience. The clinical trials included 1275 patients with dyspepsia, gastro-oesophageal reflux disorder (GORD), Irritable Bowel Syndrome (IBS), nausea and vomiting or other related conditions in 31 double-blind, placebo-controlled studies. All patients were at least 15 years old and received at least one dose of domperidone. The median total daily dose was 30 mg (range 10 to 80 mg), and median duration of exposure was 28 days (range 1 to 28 days).
On the positive side, the 31 trials were all double-blind and placebo-controlled, which is good. 1275 patients isn't a lot, but it's better than some. It also covers a wide range of conditions.
On the negative side, it was conducted by a pharmaceutical company testing their own product.
As the median duration of the 31 trials was 28 days and the maximum trial length was 28 days, we can deduce that at least 16 of the trials had a duration of 28 days.
No such deduction can be made regarding daily dosages.
My plan is to take 20mg domperidone 4 times daily at 5 hour intervals over 4 days. The reason for this is based on information in section 5.2 Pharmacodynamic Properties, in the Absorption subsection.
I plan to eat something small before each dose due to the following information also in the same section (irrelevant part omitted):
Enhanced bioavailability and increased AUC are the objective of this regimen.
As I only eat 2 small meals a day, I'll have to time these meals accordingly, and for the other 2 doses I'll eat a small snack (I'm thinking a small Snickers bar).
Additional useful information in the same section under the heading Excretion:
Domperidone is rapidly absorbed after oral administration with peak plasma concentrations occurring at approximately 1 hr after dosing. The Cmax and AUC values of domperidone increased proportionally with dose in the 10 mg to 20 mg dose range. A 2- to 3-fold accumulation of domperidone AUC was observed with repeated four times daily (every 5 hr) dosing of domperidone for 4 days.
I plan to eat something small before each dose due to the following information also in the same section (irrelevant part omitted):
The low absolute bioavailability of oral domperidone (approximately 15%) is due to an extensive first-pass metabolism in the gut wall and liver. Although domperidone's bioavailability is enhanced in normal subjects when taken after a meal...The time of peak absorption is slightly delayed and the AUC somewhat increased when the oral drug is taken after a meal.
Enhanced bioavailability and increased AUC are the objective of this regimen.
As I only eat 2 small meals a day, I'll have to time these meals accordingly, and for the other 2 doses I'll eat a small snack (I'm thinking a small Snickers bar).
Additional useful information in the same section under the heading Excretion:
The plasma half life after a single oral dose is 7-9 hours in healthy subjects...
Please feel free to comment. Any and all thoughts or ideas are welcome, and any links to other similar studies would be very useful.
If I receive more data (or can find more myself) that could improve this regimen, then I will incorporate it and create a new post if/when I plan to start.
If I receive data that would invalidate this regimen, then I will obviously not attempt to use it and will request that the thread be deleted.
Otherwise, if/when the time comes, then I will resurrect this thread and provide feedback on progress and success/failure as is appropriate.