TrumpLyftAlles | 5 points
Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats (Spain found 2020-08-26 Chaccour)Causing rhabdomyolysis by inhaling ethanol doesn't sound like a good trade off over just taking a pill / paste.
[-] TrumpLyftAlles | 1 points
rhabdomyolysis
Do you think that's really a hazard with the nebulizer?
Alcohol-induced rhabdomyolysis is a potentially life-threatening condition due to the probability of progression to acute renal injury. Patients admitted to emergency department with acute alcohol intoxication should always undergo blood and urine tests for early recognition and treatment of rhabdomyolysis.
I can't imagine this treatment lead to "acute alcohol intoxication".
doesn't sound like a good trade off
It gets the ivermectin to the lungs, where (possibly, who knows?) it would fight the virus, at higher concentrations than you would get without a BIG dose of pills/paste. I conjecture.
https://www.aafp.org/afp/2002/0301/p907.html
It's mentioned in the article as an effect on the test animals. It can be caused by extreme overexertion and dehydration, or by alcohol use. Not uncommon in people way overdoing it in a new exercise program and a very big deal. IMO getting to the right concentration if that's a side effect is not worth it and this article could actually be more ammo for too low concentration crowd.
[-] TrumpLyftAlles | 1 points
IMO getting to the right concentration if that's a side effect is not worth it
Presumably that would be observed in testing. Even rats can get drunk?! Human tests would calm the concern.
this article could actually be more ammo for too low concentration crowd
I don't see that?! What's their argument?
From the article:
The most common causes are crush injury, overexertion, alcohol abuse and certain medicines and toxic substances.
Many patients develop dialysis-dependent acute renal failure associated with the misuse of alcohol or other drugs.
You need to drink a lot for a long time to do that much damage, AFAIK.
I can't imagine nebulizing alcohol could equate to alcohol abuse; the amount of alcohol has to be negligible compared to half a fifth of whisky.
You seem to write with a lot of conviction (which is good). Do you have some personal experience with the condition, a family member or something? I don't know what your training is. Did you study it in med school?
More in a bit, but this part.. using ethanol as the vehicle is problematic IMO.
Results: There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 grams/kg in some animals.
[-] TrumpLyftAlles | 1 points
There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis
Dang, that was in the study. I passed over it without comprehension because I didn't know the word.
11 grams/kg
Didn't pay attention to that either. That's a lot. If I did my math right (always questionable), the equivalent for 210 pound me would be 37 ounces of whiskey / vodka etc. When I'm drinking (not nowadays) I might drink that much in 2-3 weeks.
[-] TrumpLyftAlles | 1 points
Interestingly, Dr. Chaccour et al are proposing a possible solution to the CONCENTRATION TOO HIGH!!! argument that has been made in a dozen or so articles, the favorite attack on ivermectin: nebulize it and breathe it into the lungs.
I need some help understanding this, the apparent punchline:
All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females.
That seems remarkable but I don't actually understand the units. 524.3 ng/g: is that relevant clinically?
#Background:
Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics.
#Methods: An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals.
#Formulation We unsuccessfully attempted to produce a water soluble-solution by combining surfactants such as polysorbate or co-solvents such as propylene glycol or glycerin. Given solubility issues and that ethanol does not interfere with ivermectin pharmacokinetics 20, ivermectin powder API was diluted in pure ethanol to reach three different concentrations, 7mg/ml, 10 mg/ml and 14 mg/ml and kept in opaque flasks at 5°C. Stability tests using HPLC conducted one week after dilution showed no changes in the original concentrations. All solutions were used within one week of preparation.
#Results: There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 grams/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs 26.2 ng/ml in the lower dose group and 152 ng/ml vs 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females.
Conclusion: Nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.
[-] TrumpLyftAlles | 1 points
pharmacodynamic
Dictionary says:
Pharmacodynamics (sometimes described as what a drug does to the body) is the study of the biochemical, physiologic, and molecular effects of drugs on the body and involves receptor binding (including receptor sensitivity), postreceptor effects, and chemical interactions.
So
Nebulized ivermectin can reach pharmacodynamic concentrations
means "can reach high enough concentrations to be effective"?
[-] thaw4188 | 2 points | Aug 27 2020 11:58:48
oh fascinating, I would really like to see if nebulized can slow/prevent lung damage more effectively and faster
especially considering how cheap it is compared to other antivirals
I've had to use glucocorticoid both in pill form and inhaled and the inhaled experience is a bit different in how it works.
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