Modulation of warfarin sodium into warfarin potassium for patients with hypertension

Prepared by/ Al-Baraa Akram De Montfort University-faculty of health and life sciences Leicester-United Kingdom I had the idea of this...

Prepared by/ Al-Baraa Akram

De Montfort University-faculty of health and life sciences

Leicester-United Kingdom

I had the idea of this research in one of the lectures which was about Cardiovascular Diseases at Assiut University in Egypt in 2017 during my study of clinical pharmacy when the lecturer told us that the anticoagulant warfarin is used in the form of warfarin sodium to facilitate its absorption, but sodium, as you know, causes an increase in blood pressure, and for most hypertensive patients, most of them are Elderly people who may suffer from a combination of chronic diseases such as heart disease and diabetes, especially those with high blood pressure.

Sodium causes increasing blood pressure, which is an undesirable problem that may occur in a hypertensive patient who suffers from blood clots, so the use of warfarin sodium may lead to an increase in his blood pressure in what is known as the famous clinical term Drug-Disease interaction.

So I thought: What if we replace sodium with potassium to get warfarin potassium, and thus avoid sodium problems for hypertensive patients?

One of you might say: Potassium causes some heart problems, and here I would like to point out that the dose of warfarin generally ranges between 1 mg to 5 mg per day, while the harmful dose of potassium is 6.5 mg per day.

Before implementing the idea in practice, I asked myself:

Which is better to replace the sodium atom with a potassium atom within this organic compound?

Is the simple substitution reaction preferred or the double substitution reaction?

1-If the simple substitution reaction was better, how can you get elementary potassium?

2- If the double replacement reaction is better, what is the concentration of potassium hydroxide required to complete the reaction? And is it better for substitution reactions or any potassium salt e.g., potassium iodide is better?

It was not easy, especially at that time when potassium was scarce in the market, so the experiment was carried out on a small scale in its infancy. I asked Dr. Noha Gamal Fekry, Assistant Lecturer at the Department of Pharmaceutical Chemistry at Sphinx University, to enlighten me on how to implement the project in practice, and then I sought the help of my sister Razan Akram,a graphic designer to design some figures which were found in introduction section for my research paper that explains the mechanism of action of warfarin. I implemented the research project in a time that took me 8 months with the help of Dr. Abdurrahman Abo El-ela, a demonstrator in the department of microbiology in Merit University.

To carry out the experiment I needed to prepare an acid like hydrochloric acid to convert ONa group into OH, filter papers, beaker, conical flask, potassium base e.g., potassium hydroxide and mortar

1-    In the mortar, grind 100 mg warfarin sodium tablets properly until you get the powder form to increase the surface area

2-    Dissolve the powder of warfarin sodium in 100 ml water and add HCl to allow sodium to substitute hydrogen and convert the ONa group into OH in the warfarin molecule according to the chemical equation

C19H15NaO4 +HCl+H2O→NaCl+ H2O+ C19H16O4

3-    Filter the solution in a filter paper to get rid of the liquid and leave the powder to dry

4-    Add the powder of warfarin back to fresh water and add potassium base as shown in chemical equation below

C19H16O4+KOH → C19H15KO4+H2O

5- Filter the solution again using a filter paper, and then leave the powder to dry to get warfarin potassium

N.B. After getting warfarin in the 3rd step, you can use organic solvent to extract warfarin only then alkalize it using potassium base (potassium hydroxide); the OH group will be ionized into OK

And in the end, Dr. Bassem Fadel - medical sales representative at Egyptian medical city Gyptopharma made the necessary spectral analysis for the warfarin potassium compound that we obtained. Of course, my project needs a further of clinical trials before its marketing and using on a large scale, but the implementation of the project, preparing it and publishing it as a research is a step on this path.

Paper link given below:-

https://globaljournals.org/GJSFR_Volume22/1-Modulation-of-Warfarin.pdf

https://globaljournals.org/GJSFR_Volume22/E-Journal_GJSFR_(G)_Vol_22_Issue_2.pdf

http://3d.globaljournals.org/Virtual_3D_GJSFR_(G)_Volume_22_Issue_2/

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Global Journals | Science Innovations & Stories Blog: Modulation of warfarin sodium into warfarin potassium for patients with hypertension
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