[Anti-psychotics and metabolism] What happens to the metabolites?

[jonnyc55]

I thought the best place to ask my question is a Biochemistry forum :).

So I have been forced to take Aripiprazole. A low dose of 5mg a day. I read that vitamin D3 is an inducer of the enzymes CYP3A4 and CYP2D6 both of which are the prime enzymes that breakdown Aripiprazole into Dehydro-Aripiprazole (an active metabolite) .

Now what happens to the Dehydro-Aripiprazole? Is that broken down even more? Or is it turned into a form that can then be excreted from the body?

I quote this : " Only after they are metabolized into more hydrophilic molecules, can they be excreted through the kidneys into the urine."

My other question to all you biologists regards the above quote, is dehydro-Aripiprazole a hydrophilic molecule? And therefore can be then excreted?

My concern is, since i have been forced to take Aripiprazole, i don't want a increase in Aripiprazole in my blood after each day or to have a horrible build up.  
Dehydro-aripiprazole also works a bit like the parent drug Aripiprazole.
I want to make sure that dehydro-aripiprazole is flushed out and that it doesn't build up. I don't want the negative toxicity effects.

Will there be an enzyme that breaks down the active metabolite dehydro-aripiprazole? Or is it now in a form that can then be excreted?  (And i hope Vitamin D3 stimulates this process.)

Thank you. 

Edited December 11, 2017 by jonnyc55
Dose correction and structure.

[jonnyc55]

So I've seen this from wiki:  

Quote

Bioavailability of the oral tablets is about 90% and the drug undergoes extensive hepatic metabolization (dehydrogenation, hydroxylation, and N-dealkylation), principally by the enzymes CYP2D6 and CYP3A4. Its only known active metabolite is dehydro-aripiprazole

and then this:

Quote

hydroxylation converts lipophilic compounds into water-soluble (hydrophilic) products that are more readily removed by the kidneys or liver and excreted

I guess the above concerns dehydro-aripiprazole, because (see below).

And then this from ncbi: 

Quote

of a highly lipophilic basic drug aripiprazole (ARPZ)

Aripiprazole is a lipophilic.

Hmm interesting. So the metabolite becomes a more readily able object to be removed? 

 

 

[John Cuthber]

6 hours ago, jonnyc55 said:

So the metabolite becomes a more readily able object to be removed? 

That's generally the case; it's part of the body's defence against toxic chemicals- make them more water soluble (by hydroxylation or conjugation with glucuronic acid or some such then get rid of them via the kidneys.

https://en.wikipedia.org/wiki/Glucuronidation

 

Don't overdo the vitamin D

https://en.wikipedia.org/wiki/Vitamin_D#Effect_of_excess

[jonnyc55]

On 12/12/2017 at 5:20 PM, John Cuthber said:

That's generally the case; it's part of the body's defence against toxic chemicals- make them more water soluble (by hydroxylation or conjugation with glucuronic acid or some such then get rid of them via the kidneys.

https://en.wikipedia.org/wiki/Glucuronidation

 

Don't overdo the vitamin D

https://en.wikipedia.org/wiki/Vitamin_D#Effect_of_excess

That is very interesting and good to know.

I will look into these functions.

Regarding vitamin D excess effects I will definitely take note. I had been taking Vitamin D3 tables (rated at 500% NRV). Would multivitamin tablets with D3 at 100% NRV prove better?

Also is there any other way to promote metabolism of aripiprazole? Or to give further aid to enzymes such as CYP3A4 and CYP2D6?

Thank you.

Edited December 14, 2017 by jonnyc55