I've read through about 70 pages now and I'm going to pop my medical 2 cents in the form of a handful of questions and statements.
1. Did anyone try dosing metronidazole more than once per day? When we dose in humans we do every 12 hours or every 8 hours depending on what bug we're covering. (This is mostly due to the metabolism half life in humans) 125 mg/10 gal is not very much drug at all from a pharmaceutical standpoint and I suspect the drug trough concentration levels are dipping rather low around the 21-23.99 hr mark before the next dose. This could have led to some of the 'resistance' some members alleged, although I'm somewhat skeptical that metronidazole-resistant dinos developed after just 3 days of dosing. Now, I saw a couple posts regarding the 'active in the water column' activity that Seachem quoted for Metroplex. When they say 'active in the water column at 48hrs', just how much drug is left in the water column? Much will be in the cells and livestock and even more will be sitting on the substrate having never hit it's intended target. This is especially true with a compound like metronidazole, which struggles to be fully soluble in water. Some will merely fall to the substrate having never really hit any targets whatsoever. When we talk drug half-lives for 'full clearance' we will typically reference the point of 3 half lives. So essentially a half of a half of a half. At that point you technically still have drug in your system, but it's such a low level as to be nearly ineffective. In humans this point is reached at roughly 24 hours +/- ~2 hours. I saw this quoted a few times as the half-life in water, which is probably not the case as there's no metabolism pathways per-se destroying the drug. What IS destroying the drug is reactions with other compounds in the water (organic and inorganic), light degradation(UV for sure and probably our standard LED/t5/MH lights) and potentially oxidative stress in the form of hydrogen peroxide as some mentioned they were dosing both together. I would be curious if Seachem had any water stability parameters or studies done to show a true drug-destruction half life in aquariums.
2. What were the results of people who dosed longer than 3 days? For the most part, we never dose metronidazole for less than 5 days in humans(rare to see 5 days even) and it's almost always 7-14 days, with 10 being very common. If DNA synthesis for cell division is merely being inhibited by the metronidazole, then it makes sense that when the drug is removed, some of the cells are able to boot their DNA/RNA encoding back up and start dividing again. Also being assumed is that the metronidazole penetrated into every single cell of dinos, which is highly unlikely. 3 days or even 10 days might not have been a long enough time to cycle out all the reproducing cells. If we're able to effectively ****** the DNA/RNA synthesis of the cell, why not dose the drug through the entire life-cycle of the protozoan to ensure 100% reproductive retardation and thus no further generations?
3. Is it possible that the metronidazole that you've dosed once per day is merely dusting the top layers of the dinos and the dinos living underneath the top layers are surviving and still reproducing due to having a 'meat shield' above them? We run into this in humans where folks will have horrible cysts or other large infections where we have to go in debride the area and greatly reduce the number of bacterial cells that the body and the antibiotics have to kill, boosting efficacy.
4. I saw several posts of people dumping large doses in out of frustration. Did this lead to any livestock issues? If no, what about taking that large dose and spreading it out over 3 doses in a day? So essentially 1/3 dosed every 8 hours.
5. When we dose metronidazole in humans for a protozoan infection, there will be some protozoan cell death due to the drug itself. However, quite a bit of the cellular death will come from the body's own immune system gobbling up and destroying the protozoan that has been rendered temporarily sterile by the drug. In the reef setting there's no immune system there to lyse the cells that are 'stunned'. Our means of lysis is removal, which twilliard touched on repeatedly. However, I feel that you need to be removing and dosing continuously for a while...possibly quite a while longer than 3-10 days.
Now, I don't really want anyone to take this as a dose your tank with 3x what you were for 3x longer than you were, but I'm curious if there was anyone out there that tried this method or something similar to it, as I feel it may have had better results.
Not trying to hijack your thread, just some stream of consciousness thoughts that I jotted down while reading through several hundred posts.
Has anyone tried dosing Metro 3 times a day and for at least 10 days like suggested above? Seems logical that it would work based on some of the results the Metro users were getting.
Sorry for the questions again @rrueger ...
1. any signs of them?
2. so if I read it correctly, your second dose- aqua-zole, you doubled the dose from 125 to 250 metro and therefore dosed a total of 1000mg for 3 days?
3. when did you add the zeovit?
4. when did you add the pods?
5. which pods did you add from algaebarn?
6. did you use the aqua-zole because it was slow to dissolve or because of other reasons?
Thanks!!!
Tomorrow I will remove the sandbed and LR. Then add a half dose of metro...then continue on using your schedule.
