Greeting :

The goal of pharmacogenomic testing for anti-Parkinson's disease drugs should be conservative and aimed at selecting determined drugs for determined patients. However, much additional research is still needed to obtain reliable pre-prescription tests.

We are ready to collaborate with your great research and my college Nusieba A Mohammed Ibrahim for any help and support.

Thank you in advance,

Dear Yahya,

Thank you for replying to my call. I have been working alone on this subject for many months now and have come to the point when it can be justified to open it up to others. My objective is to create a network of researchers each with their respective expertise and resources so that we can create more knowledge in this area as soon as possible. Only with this proven knowledge can we justify personalised medecine for Parkinson's disease, thus avoiding DDIs.

I assume that you have read my articles about CYP3A4 and levodopa on Researchgate, so I don't need to tell you what's needed. What I would like to know is where best you can help? - In which fields do you have experimental expertise and resources? What are the questions that your institution can respond to quickly and efficiently?

Best regards

Albert Wright.

I recommend you to perform a solid proof-of-concept study first, that is, prove that inhibition of CYP3A4 indeed increases the systemic exposure to L-Dopa. You do not need a placebo-group for that, but you definitely need to measure serum concentrations of L-Dopa and calculate AUC, clearance etc. Once you have that proof, you should be able to get it published in a decent neurologic/pharmacologic journal, and then there will be a lot of interest.

Dear Dr Reimers,

Thank you for your well informed reply. Of course I totally agree that what you recommend is the way forward. As you might expect from someone with no experience in this field, I have no idea of the amount of effort/resources/expertise needed to get to that level of proof. I do however share your opinion that such proof published in a decent journal would generate a lot of interest among professionals and should be the next goal.

I would very much like to discuss further with you how I/we can start to move towards developing such a project and whether you have the desire and the time to be part of a team to drive this forward.

If your response is positive, I would suggest we communicate via email or private messages on RG as a first step. My email address is given in the bio. "About the author" at the end of the posted article.

Best regards,

Albert Wright

Greetings,

I am interested with this scientific hypothesis. I want to be part project as a PhD student. We may think of the pharmacogenomics variablity among parkinsonian patients and the pharmacokinetics change via inhibition of CYP450. How ever, we lack a laboratory set up for pharmacogenomics variablity study.

regards,

Albert, if your hypothesis is right, inhibiting CYP3A4 should result in a reduced clearance of L-DOPA and, hence, in a greater AUC of its serum concentration-time curve. This can easily be shown by repeated measurements of the L-DOPA serum concentration during a 24-hour cycle. The blood samples should be taken with increasing time intervals, e.g. after 10 min, 30 min, 1 h, 4 h, 8 h, 12 h, 24 h. One set of samples with a CYP3A4 inhibitor, and one set without, 14 blood samples in total. There should be a washout period of at least 48 hours between the two sampling days. For a proof of concept, 1 subject would be sufficient. However, the more the better, as usual. The subject(s) should not take any other drugs that might affect CYP3A4. Be aware though, that an increase of L-DOPA exposure by inhibiting its breakdown is essentially the same as an increase of the L-DOPA dose. Both will result in an increased AUC of L-DOPA. Be prepared for that criticism before you present your idea to clinicians that treat Parkinson patients. If you still want to go on, message me.

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