Chloroquine Phosphate

[Dr. Reef]

I am not aware of the reason on why Wrasses dont do well in CP. But in my experience they usually quit eating which leads to death. In my experimentation I have subjected some wrasses to very low levels of CP with success but I am not confident to post that for new or novice hobbyists to try. I rather see them use copper. Low dose between 10-20mg/gal

 

[Lasse]

Do anyone know if this medication is active against the Trophont stage or only against the freeswiming stage of the ich parasite? @MnFish1 , @Nathan Milender , @HotRocks , @4FordFamily

Sincerely Lasse

 

[Nathan Milender]

Do anyone know if this medication is active against the Trophont stage or only against the freeswiming stage of the ich parasite? @MnFish1 , @Nathan Milender , @HotRocks , @4FordFamily

Sincerely Lasse

I have not come across an article reviewing the pharmacokokinetics in fish like the article you posted on prazi. I use it assuming it only works on the free stage. If it stores in the fish and/or is secreted in the fish slime I could see how it theoretically could be useful in the cyst stage. Fish gills do make a good argument for blood exposure to environmental drug but I have no idea what types or sizes of molecules can be 'inhaled'.

 

[HotRocks]

Do anyone know if this medication is active against the Trophont stage or only against the freeswiming stage of the ich parasite? @MnFish1 , @Nathan Milender , @HotRocks , @4FordFamily

Sincerely Lasse

To my knowledge it will only kill the free swimming stage so it functions the same as copper products.

 

[Lasse]

I have not come across an article reviewing the pharmacokokinetics in fish like the article you posted on prazi. I use it assuming it only works on the free stage. If it stores in the fish and/or is secreted in the fish slime I could see how it theoretically could be useful in the cyst stage. Fish gills do make a good argument for blood exposure to environmental drug but I have no idea what types or sizes of molecules can be 'inhaled'.

To my knowledge it will only kill the free swimming stage so it functions the same as copper products.

The drug is lipophilic - hence it will enter the fish blood stream from the water. Probably mostly by the gills that’s normally only have 1 - 10 cells barrier between the water and blood. Further - a saltwater fish drinks a lot - hence the concentration in the water will be the concentration they take orally. The uptake by the skin or the gills of lipophilic substances is normally a forgotten pathway but never or less it exist and have a huge importance and also the fact that salt water fish drinks is important – fresh water fish does not! Some very effective antibiotic drugs works well in saltwater but are worthless in freshwater when they are mixed with the water. why – they are water soluble (hydrophilic) and needs to be oral ingested. And they will be effective in saltwater because salt water fish drinks. However - lipophilic antibiotics mixed in the water works in fresh water because they will enter the body through the cells – best way – the gills. One example is metronidazole (flagyl) that works to treat internal flagellates in freshwater fish only with mixing into the water.

Post #4 in this thread include an interesting PDF about this drug – including its secretion. It shows up that´s in mammal rather much will be excreted by the kidneys (read the pee) but in saltwater – this pathway may be blocked IMO – because salt water fish does not pee or pee very little.

In the protocols seen here CP is dosed up to 10,5 mg/l (40 mg/Gallon)– the normal Prazi dose is 1-2 mg/l for long-term bath.

IMO – this indicate that the wrasses sensitivity for CP can be linked to a to high blood content of the drug in time. If the drug is rather stable in the water during time – the pathway with lipophilic uptake will rise and rise and rise the blood content if they swim in the same concentration. The drug will be bio-accumulated. Further on – I do not hold it impossible that the drug can be effective even against the Trophont stage because there will be therapeutic levels in bloodstream by time.

If someone have the gut to test with a Prazi like concentration of CP (1-2 mg/l) during 30 days we would know and maybe we will have a much better treatment method against ICH compared with today

Sincerely Lasse

 

[MnFish1]

Do anyone know if this medication is active against the Trophont stage or only against the freeswiming stage of the ich parasite? @MnFish1 , @Nathan Milender , @HotRocks , @4FordFamily

Sincerely Lasse

I believe its mostly the free-swimming theronts.

 

[Nathan Milender]

The drug is lipophilic - hence it will enter the fish blood stream from the water. Probably mostly by the gills that’s normally only have 1 - 10 cells barrier between the water and blood. Further - a saltwater fish drinks a lot - hence the concentration in the water will be the concentration they take orally. The uptake by the skin or the gills of lipophilic substances is normally a forgotten pathway but never or less it exist and have a huge importance and also the fact that salt water fish drinks is important – fresh water fish does not! Some very effective antibiotic drugs works well in saltwater but are worthless in freshwater when they are mixed with the water. why – they are water soluble (hydrophilic) and needs to be oral ingested. And they will be effective in saltwater because salt water fish drinks. However - lipophilic antibiotics mixed in the water works in fresh water because they will enter the body through the cells – best way – the gills. One example is metronidazole (flagyl) that works to treat internal flagellates in freshwater fish only with mixing into the water.

Post #4 in this thread include an interesting PDF about this drug – including its secretion. It shows up that´s in mammal rather much will be excreted by the kidneys (read the pee) but in saltwater – this pathway may be blocked IMO – because salt water fish does not pee or pee very little.

In the protocols seen here CP is dosed up to 10,5 mg/l (40 mg/Gallon)– the normal Prazi dose is 1-2 mg/l for long-term bath.

IMO – this indicate that the wrasses sensitivity for CP can be linked to a to high blood content of the drug in time. If the drug is rather stable in the water during time – the pathway with lipophilic uptake will rise and rise and rise the blood content if they swim in the same concentration. The drug will be bio-accumulated. Further on – I do not hold it impossible that the drug can be effective even against the Trophont stage because there will be therapeutic levels in bloodstream by time.

If someone have the gut to test with a Prazi like concentration of CP (1-2 mg/l) during 30 days we would know and maybe we will have a much better treatment method against ICH compared with today

Sincerely Lasse

I think it would be a worthwhile experiment. I do not have the facilities to test tissue and blood concentrations of chloroquine. It would also be useful to have a water test of chloroquine concentration to measure the ongoing concentration considering the article on bacterial metabolism. I have been a bit sloppy with my chloroquine dosing as I start at the recommended dosing. It is difficult to let the fish sit an entire QT cycle with a sponge filter and no water changes so I tend to err on the higher side with water changes. Twenty gallons is not that large of tank so I suspect my concentration rises towards the end minus what is eaten. I allowed this because of the forgiving index on chloroquine. This may attribute to the success I have had, or it could just be luck.

I was surprised to see the detail on the aquafarming fish article but that industry does have a bit more economic incentive. I am not sure it explains the wrasse's sensitivity. I have a flasher in it right now that is doing fine (although did have an issue early on and is in an extended timeframe QT). You would think fish of similar size and metabolism would have similar tolerances. I suspect there is some other aspect to this, likely liver or renal metabolism variation. I do not suppose you have an article laying around addressing comparative GFR of fish or liver enzyme complexes? I have been looking into veterinary texts but I have not found anything that looked promising enough to purchase. The local university has a vet school, I was thinking about peeking at their required texts for any fish courses and see what they are promoting.

 

[MnFish1]

I think it would be a worthwhile experiment. I do not have the facilities to test tissue and blood concentrations of chloroquine. It would also be useful to have a water test of chloroquine concentration to measure the ongoing concentration considering the article on bacterial metabolism. I have been a bit sloppy with my chloroquine dosing as I start at the recommended dosing. It is difficult to let the fish sit an entire QT cycle with a sponge filter and no water changes so I tend to err on the higher side with water changes. Twenty gallons is not that large of tank so I suspect my concentration rises towards the end minus what is eaten. I allowed this because of the forgiving index on chloroquine. This may attribute to the success I have had, or it could just be luck.

I was surprised to see the detail on the aquafarming fish article but that industry does have a bit more economic incentive. I am not sure it explains the wrasse's sensitivity. I have a flasher in it right now that is doing fine (although did have an issue early on and is in an extended timeframe QT). You would think fish of similar size and metabolism would have similar tolerances. I suspect there is some other aspect to this, likely liver or renal metabolism variation. I do not suppose you have an article laying around addressing comparative GFR of fish or liver enzyme complexes? I have been looking into veterinary texts but I have not found anything that looked promising enough to purchase. The local university has a vet school, I was thinking about peeking at their required texts for any fish courses and see what they are promoting.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734797/

Here is a tidbit - in freshwater...

 

[Lasse]

Thank you!

Read it through and it confirmed my concerns. However – Is very unclear which concentration they have used. In the abstract and from chapter 2.4 they use mg/ml which is 1000 time weaker than mg/l – however in chapter 2,2 and 2.3 they use mg/l, further in the appendix they use ppm – which is equal to mg/l in this case. I have written to the main author and ask about this – if there is something I miss or if it is a typo. If they mean mg/l – all should probably stop dosing 10 ppm to our salt watyer fish and that protocol should not be used IMO. The histological damage is huge in this test run and in that case - if the real concentration is 3.2 ppm during 35 days. Thats we do not know for the moment - but I suspect that mg/ml is wrong and a typo


The tested animal Cyprinus carpio is among one of the must toughest fish I have handled - only the African catfish Clarias gariepinus is tougher IMO. That fish you can´t even kill with a hammer – believe me – I have tried


But it does not matter (the concentrations) in the long run - the drug is lipophilic and together with time – it will concentrate in the body of the fish – it means that even a low water concentration will bioaccumulate into the fish and mostly in the fatty parts of the body. It is not a matter of plain equilibrium – the fat in the fish will “suck” up every lipophilic substance with time in the water. What I understand – the sensitivity among the wrasses is depended of the length of the exposure period with the commonly used concentrations. Of course – the concentration in the water of lipophilic drugs have an importance – but only if you take with a timeframe. Let us say that you want x nanogram/l in the bloodstream of a fish. You can achieve this with two different strategies – high water concentration – short exposure time or low water concentrations – long exposure time.


The article @MnFish1 dig up show that the drug will be transported into the fish from the surrounding water and will be able to reach concentrations that will damage certain organs inside the fish. When it finally in the fish – it will be broken down and the normal pathway for this is by a cascade enzyme system known as MFO (Mixed Function Oxidase). The main goal for this system is to transfer lipophilic substances into smaller substances and preparing for other system to make them more hydrophilic - hence be able to further transport out from the body. These processes take mainly place in the liver and kidney. The MFO system is fascinating – it has an ability to change its active enzymes in order to manage new compounds and old enzymes can act against new compounds – but the result – the metabolite - can be a more toxic substance.


Now we will come to a rather interesting thing – the excretion time. As I can see in the article, I linked to in #4 – the excretion is mainly through the kidneys and through the pee. Because of osmotic reasons – saltwater fish does not pee so much and if they do – it is vey concentrated. IMO – there is a reason to believe that QP (and its metabolites) will have a longer residence time in saltwater fish compared with other animals. I.e. – if there is a therapeutic concentration of QP in the body fluids against the ich parasite it can be enough with a dip in a certain concentration of QP to maintain that concentration for a prolonged period.


Is there a therapeutic concentration of QP in the body fluids against ich parasite (and maybe velvet) – with other words – can QP be active against the Trophont stage?


I think that you can just get an idea from these descriptions of this stage:

2) Feeding

Once the Theront finds a host, it attaches and is now called a Trophont. The Trophont burrows into the fish and consumes the flesh. This is the stage at which infection is evident as little white salt sized dots on the fish's skin

The trophont is the “feeding stage,” during which the parasite is found embedded within the tissues of the fish

A short note on the sensitivity of the wrasses. I think that the gills is the main pathway for uptake of lipophilic substances but fishes with small scales or non, maybe will take up these substances faster than other fish, hence get lethal blood concentrations faster.


Sincerely Lasse

 

[Nathan Milender]

Thank you!

Read it through and it confirmed my concerns. However – Is very unclear which concentration they have used. In the abstract and from chapter 2.4 they use mg/ml which is 1000 time weaker than mg/l – however in chapter 2,2 and 2.3 they use mg/l, further in the appendix they use ppm – which is equal to mg/l in this case. I have written to the main author and ask about this – if there is something I miss or if it is a typo. If they mean mg/l – all should probably stop dosing 10 ppm to our salt watyer fish and that protocol should not be used IMO. The histological damage is huge in this test run and in that case - if the real concentration is 3.2 ppm during 35 days. Thats we do not know for the moment - but I suspect that mg/ml is wrong and a typo


The tested animal Cyprinus carpio is among one of the must toughest fish I have handled - only the African catfish Clarias gariepinus is tougher IMO. That fish you can´t even kill with a hammer – believe me – I have tried


But it does not matter (the concentrations) in the long run - the drug is lipophilic and together with time – it will concentrate in the body of the fish – it means that even a low water concentration will bioaccumulate into the fish and mostly in the fatty parts of the body. It is not a matter of plain equilibrium – the fat in the fish will “suck” up every lipophilic substance with time in the water. What I understand – the sensitivity among the wrasses is depended of the length of the exposure period with the commonly used concentrations. Of course – the concentration in the water of lipophilic drugs have an importance – but only if you take with a timeframe. Let us say that you want x nanogram/l in the bloodstream of a fish. You can achieve this with two different strategies – high water concentration – short exposure time or low water concentrations – long exposure time.


The article @MnFish1 dig up show that the drug will be transported into the fish from the surrounding water and will be able to reach concentrations that will damage certain organs inside the fish. When it finally in the fish – it will be broken down and the normal pathway for this is by a cascade enzyme system known as MFO (Mixed Function Oxidase). The main goal for this system is to transfer lipophilic substances into smaller substances and preparing for other system to make them more hydrophilic - hence be able to further transport out from the body. These processes take mainly place in the liver and kidney. The MFO system is fascinating – it has an ability to change its active enzymes in order to manage new compounds and old enzymes can act against new compounds – but the result – the metabolite - can be a more toxic substance.


Now we will come to a rather interesting thing – the excretion time. As I can see in the article, I linked to in #4 – the excretion is mainly through the kidneys and through the pee. Because of osmotic reasons – saltwater fish does not pee so much and if they do – it is vey concentrated. IMO – there is a reason to believe that QP (and its metabolites) will have a longer residence time in saltwater fish compared with other animals. I.e. – if there is a therapeutic concentration of QP in the body fluids against the ich parasite it can be enough with a dip in a certain concentration of QP to maintain that concentration for a prolonged period.


Is there a therapeutic concentration of QP in the body fluids against ich parasite (and maybe velvet) – with other words – can QP be active against the Trophont stage?


I think that you can just get an idea from these descriptions of this stage:






A short note on the sensitivity of the wrasses. I think that the gills is the main pathway for uptake of lipophilic substances but fishes with small scales or non, maybe will take up these substances faster than other fish, hence get lethal blood concentrations faster.


Sincerely Lasse

I think it mostly alleviated my concerns. I do agree the concentration discrepancy needs to be addressed as it makes a huge difference in what dosing we are dealing with. If it turns out that their lethal dose is really 31 mg a ml I think what is happening in QT has a wide margin of safety. Short of dropping a bag into an aquarium I think it is unlikely that dose will be seen. Everything that has an effect has the potential to be toxic at the wrong dose or in the wrong circumstance. You never get anything without some risk. Even if it ended up being 3 mg/ml it still equates to over 11 grams per gallon which is also much higher then suggested QT dosing. If it is 31 mg per liter the index narrows a lot more.

The liver markers can be alarming when you see them on paper. I do not have a feel for how these operate in fish. If this were a person I would not be alarmed by a less than 2-fold increase over normal when I know the source is a short term medication. Again, risk vs benefit is a value judgement. Typically, a dangerous acute toxicity will raise these from 40s to at least several hundreds if not near a thousand.

The histological data is interesting, but I again found their data presentation a little confusing. The graph starts with control and then lists what I assume are days following. Regardless, there is an increase in damage and then a recovery down the road. It would have made more sense to me to have histological samples for control, sub-lethal, and lethal dosing comparing within each group over time. If I read this correctly it is not surprising these effects appear to be reversible. It is also possible I did not read it correctly.

I need to review your article number four, I think I lost that one in the shuffle.

 

[Lasse]

Important is that this study is done with chloroquine (C18H26CIN3) not with chloroquine phosphate (C18H29ClN3.H3PO4), hence it can be some smaller diferences between the concentrations. But I´m rather sure that the LC50 was in mg/l. But I hope they comeback to me with the right value. The most important thing here - IMO - is that the drug will enter the fish and probably bioackumulate if the concentration is stable on the outside. And there is reports of lethargy and mortality of som SW species after a prolonged tratment period. To swim in water with a lipophilic drug is (IMO) like a constant small oral intake. The inside concentration will be skyrocket compared with the outside after a while.

Sincerely Lasse

 

[Lasse]

The graph starts with control and then lists what I assume are days following. Regardless, there is an increase in damage and then a recovery down the road. It would have made more sense to me to have histological samples for control, sub-lethal, and lethal dosing comparing within each group over time. If I read this correctly it is not surprising these effects appear to be reversible. It is also possible I did not read it correctly.

I´m sorry to say but I read the tables in a different way - the 96 H is the LC50 test, the 7 - 35 coloums refer to days of the sublethal tests, they have done several investegation during the 35 day long sublethal test. It does not show a reversible effect - it is different tests. But confusing - yes a little - have to read it twice.

I got a reply from the authors of the article - it is - as I suspected - it is a typo. LC 50 was really 31.62 mg/l (31.62 ppm). The sublethal test was done in 3.16 mg/l (3.16 ppm). As I said before – common carp is known to be very though. I think this is alarming and I would not use QP with the doses that are in use for the moment. Around 33 % of the today recommended dose (that is 40 mg/Gallo that´s around 10 ppm (10 mg/l) have shown to cause serve effects both in gills, liver and kidneys in at least on fishspecies.

However - I suspect that the drug also is able to kill the encysted forms (encysted in the fish) - a lower dose or a dip in a high dose could be effective.

Sincerely Lasse

 

[robdareefer]

Question how come in article treating fish that are expected to have ick for 30 days, then at bottom it says treat fish know with ick for only 15 days? Is there a reason?

 

[Dr. Reef]

in some cases after 15 days i have noticed fish being lethargic and non responsive. if that state happens then treat for 15 days, move to sterile tank and observe and if needed run CP again. Otherwise full 30 days.

 

[Halal Hotdog]

This is very interesting. I have had success with 40mg/gallon and have noticed lethargy after a week or so. 60mg/gallon ended in disaster, all the fish stopped moving. Had to move them to non-treated tank for them to survive.
Based on this, is there a new recommended treatment dosage of CP in QT?

 

[Dr. Reef]

This is very interesting. I have had success with 40mg/gallon and have noticed lethargy after a week or so. 60mg/gallon ended in disaster, all the fish stopped moving. Had to move them to non-treated tank for them to survive.
Based on this, is there a new recommended treatment dosage of CP in QT?

I have seen 100% cure as low as 20mg/gal
I personally dont go over 40mg/gal for reasons you yourself experienced.

 

[Halal Hotdog]

I have seen 100% cure as low as 20mg/gal
I personally dont go over 40mg/gal for reasons you yourself experienced.

That is great to hear, I have some fish coming, will try 20mg/gallon. I had a feeling the dosage was too high, however had no basis except my individual experience.

 

[Dr. Reef]

Honestly there is no real hard proof on CP and its dose or how it works or how much it degrades etc. No test kit to measure. It's all theories so far.
But in my personal experience I have been using cp for over 5 yrs now. I have seen mild infections going away in 10mg/gal and average ich infections gone at 20mg/gal.
40mg/gal is the max I practice.
Even at 40mg I notice past 2 weeks fish stops eating, becomes lethargic and almost to a point where i am afraid i will lose it.

 

[Halal Hotdog]

Honestly there is no real hard proof on CP and its dose or how it works or how much it degrades etc. No test kit to measure. It's all theories so far.
But in my personal experience I have been using cp for over 5 yrs now. I have seen mild infections going away in 10mg/gal and average ich infections gone at 20mg/gal.
40mg/gal is the max I practice.
Even at 40mg I notice past 2 weeks fish stops eating, becomes lethargic and almost to a point where i am afraid i will lose it.

This is exactly what I was seeing at 40mg/gallon

 

[Halal Hotdog]

Is there a dosage where you have not had success treating a fish? For example, have you run 10mg/gallon and after treatment the fish still presented with parasites?