I've reduced Darcy's Cabergoline dose to EOD

Suzanne & Darcy

Suzanne & Darcy

Very Active Member
For now, with Darcy's unexplained kidney problems coming up so unexpectedly after previously excellent kidney values, I have reduced Darcy's Cabergoline dose to every other day instead of every day. I have no idea whatsoever if Cabergoline had anything to do with sending him into renal failure. The vet says that she searched the available literature and couldn't find anything to indicate that it did.

I'm just trying to give his kidneys a break since it is a medication and it has to be excreted from the body somehow. Now, as to that, I have been trying to read whether Cabergoline is excreted through the liver or the kidneys. I'm not sure, but I thought I read something about the liver? If anybody has any information on this, I would appreciate it. @Larry and Kitties ? Do you know anything about this.

It is frustrating that some of the Cabergoline research is unpublished (from that Vet. in Colombia, right?) Many of the studies have been small and of short duration.

Oh, and the EOD dosing may be why his BG numbers are starting to climb. For now, until I get the kidney function values down, I'm going to have to manage it.
 
Suzanne & Darcy said:
I'm just trying to give his kidneys a break since it is a medication and it has to be excreted from the body somehow. Now, as to that, I have been trying to read whether Cabergoline is excreted through the liver or the kidneys.
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In humans it is metabolized vial the live and excreted via the kidneys/urine

Metabolism
Hepatic. Cabergoline is extensively metabolized, predominately via hydrolysis of the acylurea bond of the urea moiety. Cytochrome P-450 mediated metabolism appears to be minimal. The main metabolite identified in urine is 6-allyl-8b-carboxy-ergoline (4-6% of dose). Three other metabolites were identified urine (less than 3% of dose).

Route of elimination
After oral dosing of radioactive cabergoline to five healthy volunteers, approximately 22% and 60% of the dose was excreted within 20 days in the urine and feces, respectively. Less than 4% of the dose was excreted unchanged in the urine.

Half-life
The elimination half-life is estimated from urinary data of 12 healthy subjects to range between 63 to 69 hours.

https://go.drugbank.com/drugs/DB00248

I could not find anything about any adverse effects on the kidneys.
 
Larry and Kitties said:
In humans it is metabolized vial the live and excreted via the kidneys/urine

Metabolism
Hepatic. Cabergoline is extensively metabolized, predominately via hydrolysis of the acylurea bond of the urea moiety. Cytochrome P-450 mediated metabolism appears to be minimal. The main metabolite identified in urine is 6-allyl-8b-carboxy-ergoline (4-6% of dose). Three other metabolites were identified urine (less than 3% of dose).

Route of elimination
After oral dosing of radioactive cabergoline to five healthy volunteers, approximately 22% and 60% of the dose was excreted within 20 days in the urine and feces, respectively. Less than 4% of the dose was excreted unchanged in the urine.

Half-life
The elimination half-life is estimated from urinary data of 12 healthy subjects to range between 63 to 69 hours.

https://go.drugbank.com/drugs/DB00248

I could not find anything about any adverse effects on the kidneys.
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Thank you, Larry! You are a wealth of knowledge!
 
Here is a quote from an email with Chris Scudder (then at RVC) when I first asked about cabergoline when he was looking for candidates for their trial - I was wondering if it was an option for Neko:
We would like cats to have an echocardiogram if possible prior to starting medication but we understand this may not be possible for all. The main risk of cabergoline is its potential to promote fibrosis and leaky heart valves. The current risk in human medicine is deemed to be low based on the most recent study describing people who have received the drug for 5 consecutive years on a daily basis. There are no reports that I am aware of which describe cabergoline causing hypertrophic cardiomyopathy (HCM) in people, which is important as HCM is the most common form of heart disease in cats. However, having said that, we do not know the risk in cats. I agree that Neko may not be a suitable candidate for this reason given her past, although if her heart disease was an acute event and now resolved I wouldn’t be absolute on that as the only alternative effective medication that we currently know about is pasireotide which is not feasible due to cost in many cases. However, this is the reason why we like to speak to veterinarians about any potential case to try to find out these significant prior ill-healths in their medical histories.
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One other thought, you could always contact either the folks at the South American Study or the Diabetes Remission Clinic at RVC, to see if they have any information.
 
Wendy&Neko said:
One other thought, you could always contact either the folks at the South American Study or the Diabetes Remission Clinic at RVC, to see if they have any information.
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I would be willing to contact them to make inquiries. Where can I find their contact information.

I am doubtful that this was caused by Cabergoline, but I am just trying to be cautious right now. I pray that this kidney problem will be able to heal as it has not started or progressed like ordinary kidney disease. I just don't know what could have caused it. I spent a huge portion of my day entering lab values for Darcy going back to June of last year when he was first diagnosed. He had remarkably good kidney values. Even when he was in the hospital with a DKA and Hepatic Lipidosis September 27 - October 3, his kidney function tests were excellent. I can look back at my spreadsheet and look at some of my old posts where I am remarking about his appetite declining... it's somewhere in there in the last month or six weeks. Thanks for your insight, Wendy. It is always appreciated!
 
If Darcy’s kidney disease is a result of the Acromegaly itself, then I could actually be harming him and making things worse by reducing the Cabergoline?

Or, if his kidneys are not doing an efficient job of clearing the medication because they are impaired, then he could be retaining too much of the Cabergoline in his system for too long of a period of time.
It’s hard to know what to do and clearly my vet has no experience with Cabergoline so she doesn’t know either.
 
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Larry and Kitties said:
In humans it is metabolized vial the live and excreted via the kidneys/urine

Metabolism
Hepatic. Cabergoline is extensively metabolized, predominately via hydrolysis of the acylurea bond of the urea moiety. Cytochrome P-450 mediated metabolism appears to be minimal. The main metabolite identified in urine is 6-allyl-8b-carboxy-ergoline (4-6% of dose). Three other metabolites were identified urine (less than 3% of dose).

Route of elimination
After oral dosing of radioactive cabergoline to five healthy volunteers, approximately 22% and 60% of the dose was excreted within 20 days in the urine and feces, respectively. Less than 4% of the dose was excreted unchanged in the urine.

Half-life
The elimination half-life is estimated from urinary data of 12 healthy subjects to range between 63 to 69 hours.

https://go.drugbank.com/drugs/DB00248

I could not find anything about any adverse effects on the kidneys.
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Yes. I am pretty sure that is why I read that in compromised kidneys the dose should be reduced. I don't know what the elimination half-life is in cats? Maybe nobody has ever checked this.
 
Just in case this is of any help:

Cabergoline Dosing as Per Dr. Scudder et al.most recent Pilot Study (Christopher J Scudder et al. J Feline Med Surg. 2021 Feb.)—-

“There are no published studies describing the pharmacokinetics of cabergoline in cats. The plasma elimination half-life is between 63 to 109h in humans (8). The initial dose of 5μg/kg q24h by mouth was chosen because this was the licensed dose for the treatment of inappropriate lactation in cats, and this dose was effective in terminating pregnancy in queens, which suggests effective suppression of prolactin secretion.19 This dose is equivalent to a 0.5 mg q24h dose for an average human using mg/kg dosing, which is reported to result in GH suppression in humans with acromegaly.20 However, other studies have reported using higher doses of cabergoline to treat cats and the medication was well tolerated, and some humans with acromegaly require higher doses to achieve a biochemical response.21,22 This was part of the rationale for increasing the initial cabergoline dose from 5 to 10 μg/kg q24h for cats 4–9”

Another thought or question worth asking an endocrinologist who treats a significant amount of HST in cats, specific to kidneys, is have they seen underlying CKD being masked &/or potentially masked intermittently in labs secondary to the excessive growth hormone similar to what occurs with cats who have hyperthyroidism (different hormone, but similar effects on the kidneys GFR & RPF)?Excessive GH effects the kidneys ....specifically the glomerular filtration rate (GFR) & Renal Plasma Flow (RPF) & it is likely that if 1) the tumor is pulsing less GH at one time &/or 2) the Cabergoline decreases hormone secretion in your cats particular subtype of tumor, the effects on the kidneys GFR and RPF would be decreased resulting in the unmasking of any underlying kidney issue. The opposite would occur if the tumor is pulsing more.....the issue would be masked so the labs would improve—albeit artificial & time limited improvement.
 
Diane and Kierra said:
Suzanne - I invited you to an April conversation with @Tillie and Valentino who is able to contact Dr. Elber about the south American study through "Researchgate"

prayers for Darcy :bighug:
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I just saw that. Thank you so much. I just replied! This is awesome. Read what I wrote and tell me what you think. This has helped me put some more of my thoughts together. I am going to formulate a post on the Acro forum with all of my musings on this topic. Just been soooo busy taking care of my sweet boy!
 
Yes please, if you folks find out anything of general interest to people about cabergoline, I'd love to see a post here about it.

If you are interested in how HST impacts the kidneys, I have an article for you, see attached. It is about people, but there is probably a lot of commonality. It does say that the kidney is one organ that has little research in relation to acromegaly.
 

Attachments

Thank you. I believe it affects GFR. It’s complicated though. I’ve been doing a lot of reading. We definitely will share info for you and everyone on the Board. I think that @Tillie and Valentino has perhaps already shared what she found out from Dr Eber when she contacted him through Researchgate.
 
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