Minocycline Data

Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
Joe Ham
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Location: New Mexico, USA

Minocycline Data

Post by Joe Ham » Mon 21 Jan 2008 22:25

HIGHLIGHTS Acid stable, good BBB, BID dosing, active against CWD form, some evidence that it is useful in reducing the effects of Alzheimer's disease,
http://www.lymeneteurope.org/forum/view ... ?f=6&t=597

[Edit to remove the comment that Mino has poor intracellular penetration, see below. I don't know where I got that idea, but Martian caught it. Thanks, Martian.]

TRADE NAMES Minocycline, Mino, Minocin, Arestin

FAMILY Tetracyclines

FORM Tabs and caps

MODE OF ACTION B'static, binds to 30s ribosomal subunit to inhibit protein synthesis. Effect is also on the L-form of Bb. The higher "Lyme" dosages, >400 mg per day, may act b'cidal but with increased likelihood of side effects.

ABSORPTION up to 90% PO, can take with food, absorption decreased with antacids containing Al, Ca, Mg, Fe, Zn. Mineral supplements should be taken 4 hrs away from dose. Not just before bed.

MOLECULAR WEIGHT 494

METABOLISM Liver, kidney

ELIMINATION bile, urine, feces

BIOAVAILABILITY 60 to 90%, rather high individual variability, sometimes serum level is tested to insure adequate dosage, food reduces bioavailability slightly (~20%)

TISSUE PENETRATION High lipid solubility, good CNS penetration, 2 to 3 times better than Doxy, 10 times better than Tetracycline.

SERUM PEAK 1 to 4 hrs. Delayed 1 hr with food but AUC unchanged.

HALF LIFE 16 to 20 hrs.

DOSAGE 200 mg loading, then 100 mg bid, Lymies often ramp up, especially if high bacterial load is suspected, sometimes to higher dosage if tolerated, then monitor liver and kidney enzymes closely.

MIC / MBC very dependent on the organism, testing is sometimes recommended

INDICATIONS Lyme, also indicated for Mycoplasma, Chlamydia, Acne

CONTRAINDICATIONS Pregnancy, children <8 yrs

DRUG INTERACTIONS Cholestyramine, sodium bicarbonate, warfarin

ALLERGIC REACTION treat with methylprednisolone 1g/d [! ?]

SIDE EFFECTS Photosensitivity but less than Tetracycline, varying degrees of GI reactions, nausea, diarrhea, vomiting, vertigo (more common in women), colitis (Clostridium difficile), Candida superinfectons, antianabolic problems if renal insufficiency, excessively high blood levels may cause fatal acute fatty degeneration of liver. Outdated tetracyclines can degenerate and cause Fanconi's syndrome, (glucose, amino acids, phosphates in urine)

IMMUNE SUPPRESSION yes, slight to moderate which may reduce painful inflammation but may also allow non-susceptible bacteria to flourish

COST about $1 or less per 100 mg tab

MORE DETAILS:
http://www.rxlist.com/cgi/generic/minocycline_cp.htm
http://www.drugs.com/pro/minocycline.html
Last edited by Joe Ham on Mon 4 Feb 2008 17:30, edited 1 time in total.

Martian
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Re: Minocycline Data

Post by Martian » Mon 21 Jan 2008 22:57

Joe Ham wrote:HIGHLIGHTS Acid stable, good BBB, BID dosing, active against CWD form but poor intracellular penetration
Intracellular penetration of minocycline does not seem to be poor:

Quote from "LATE AND CHRONIC LYME DISEASE" by Sam T. Donta, MD:

"In evaluating the possible factors, it would appear that antibiotics that can
achieve intracellular concentrations and activity are the most efficacious
drugs. The results of studies in Klempner’s laboratory using a tissue
culture model of borrelia infection demonstrated that ceftriaxone was incapable
of eradicating intracellular organisms (17); similar experiments in Raoult’s
laboratory using an endothelial cell model demonstrated that tetracycline and
erythromycin were effective, but beta lactam antibiotics were not (3). These
results are in line with our experience that the tetracyclines and macrolides
achieve the greatest success. In contrast to beta lactams, antibiotics of the
tetracycline and macrolide classes are capable of good intracellular
penetration.
"

Here is a supporting study: (free full text)

Antimicrob Agents Chemother. 1994 May;38(5):1059-64.

Antibiotic penetration of and bactericidal activity within endothelial cells.
Darouiche RO, Hamill RJ.

Infectious Disease Section, Veterans Affairs Medical Center, Houston, Texas 77030.

It has been observed that the number of cases of infective endocarditis arising in patients who have no previous identifiable cardiac abnormalities is increasing, suggesting that direct bacterial interactions with endothelium may occur. Furthermore, the prolonged natural history of endocarditis, need for lengthy therapy, and frequency of relapse suggest that intracellular bacteria that may be protected from antimicrobial action and host responses exist. Using high-performance liquid chromatography, we investigated the penetration of seven antibiotics used to treat Staphylococcus aureus infections into cultured human umbilical vein endothelial cells and the effect of these antibiotics on the intracellular killing of two strains of the organism. In general, endothelial cell penetration of lipophilic drugs, such as minocycline, ciprofloxacin, and rifampin, exceeded that of hydrophilic drugs, represented by nafcillin, cefazolin, cefuroxime, and vancomycin. Bacterial killing paralleled the intracellular penetration of all the antibiotics except rifampin, which concentrated well inside cells but had poor killing activity. However, when combined with the other antibiotics, rifampin potentiated their killing activity against intracellular S. aureus.

PMID: 8067738 [PubMed - indexed for MEDLINE]

Joe Ham
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Location: New Mexico, USA

Re: Minocycline Data

Post by Joe Ham » Tue 22 Jan 2008 5:39

Thanks, Martian,
I may have seen those papers before but probably forgot them and the importance of the comments on Tetras and Macrolides. Good that you reminded me.

That seems to explain my recent experience with Ceftin. It pulled me out of two relapses very quickly but the effect didn't last very long after I stopped taking it. Ceftin is recommended as first line oral by both IDSA and ILADS. Strange.

I got more "milage" from Rulid or Zithro and Flagyl but that was about a year ago and my whole system may have been different then, or so it seems.

An interesting finding in the full PDF of that paper was that Cipro and Rifampin have not only good cellular penetration but also accumulation. They didn't look at the macrolides but that property of the macrolides, especially Zithro, has been presented in other papers.


I noticed that Minocycline is supposedly acid stable. So is there any advantage to combining with Plaquenil as an intracellular alkalizer? Both are said to be immune suppressive, but as usual those reports failed to specify which facet of the very complex immune system was affected. It would help to know if the effects are independent or synergistic.

cave76
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Re: Minocycline Data

Post by cave76 » Tue 22 Jan 2008 16:01

Joe said:

***That seems to explain my recent experience with Ceftin. It pulled me out of two relapses very quickly but the effect didn't last very long after I stopped taking it.****

How long did you take it for?

Joe Ham
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Re: Minocycline Data

Post by Joe Ham » Mon 4 Feb 2008 19:58

Cave76 wrote:
***How long did you take it for? ***

Readers should be aware that cave76 and I have equal respect for the proven efficacy of antibiotics for treating (suppressing) the late (chronic) stage of Lyme disease.

However, Cavey favors continuos long term application, whereas I try to walk the line between symptoms and side effects by intermittent courses. But the rationale for each approach would be better done on a different thread, a very long one no doubt.

******************************************

An interesting series of articles on Mino was posted last April to .sci.med (before it had turned completely into the sewer that it is now.) The first reference, 1991, is the earliest that I could find that indicates intracellular location of Bb and therefore the need for intracellular activity of an antibiotic.

1991
http://iai.asm.org/cgi/reprint/59/2/671.pdf

2000
http://groups.google.ms/group/sci.med.d ... 698ceba898

2004
http://groups.google.ms/group/sci.med.d ... d4c0d9390a

2005
http://groups.google.ms/group/sci.med.d ... 83e7584423

Joe Ham
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Re: Minocycline Data

Post by Joe Ham » Thu 7 Feb 2008 5:18

Minocycline Attenuates Neuronal Cell Death and Improves Cognitive Impairment in Alzheimer's Disease Models.

Neuropsychopharmacology. 2007 Apr 4

Choi Y ,Kim HS ,Shin KY ,Kim EM ,Kim M ,Kim HS ,Park CH ,Jeong YH ,Yoo J ,Lee JP ,Chang KA ,Kim S , Suh YH .

1Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea.

Minocycline is a semi-synthetic tetracycline antibiotic that effectively crosses the blood-brain barrier. Minocycline has been reported to have significant neuroprotective effects in models of cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, and Huntington's and Parkinson's diseases.

In this study, we demonstrate that minocycline has neuroprotective effects in in vitro and in vivo Alzheimer's disease models.
Minocycline was found to attenuate the increases in the phosphorylation of double-stranded RNA-dependent serine/threonine protein kinase, eukaryotic translation initiation factor-2 alpha and caspase 12 activation induced by amyloid beta peptide(1-42) treatment in NGF-differentiated PC 12 cells. In addition, increases in the phosphorylation of eukaryotic translation initiation factor-2 alpha were attenuated by administration of minocycline in Tg2576 mice, which harbor mutated human APP695 gene including the Swedish double mutation and amyloid beta peptide(1-42)-infused rats.

We found that minocycline administration attenuated deficits in learning and memory in amyloid beta peptide(1-42)-infused rats.

Increased phosphorylated state of eukaryotic translation initiation factor-2 alpha is observed in Alzheimer's disease patients' brains and may result in impairment of cognitive functions in Alzheimer's disease patients by decreasing the efficacy of de novo protein synthesis required for synaptic plasticity.

On the basis of these results, minocycline may prove to be a good candidate as an effective therapeutic agent for Alzheimer's disease.

Neuropsychopharmacology advance online publication, 4 April 2007; doi:10.1038/sj.npp.1301377.

PMID: 17406652 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/1740 ... PlusDrugs2

itsy
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Re: Minocycline Data

Post by itsy » Thu 7 Feb 2008 14:41

JOe...

Wonderful. This is just the kind of thing I have been looking for, thanks.

I take this stuff.

I find it (and tetracycline) greatly greatly helped my narcolepsy...to the point it is ALMOST completely gone. I know narcolepsy seems to be a problem with the hypocreitian (sp?) transmitters from chronic inflammation in some part of the brain (I know, my scientic spelling and knowledge is staggering), and that they also find this in some parkinson's patients.

I have been wondering if my continued benfit from Mino is that it is the first thing that has crossed the BBB and that it actually kills or controls the BB...OR if it is just this neuro-protective action that is giving me benefit.

ANY idea the long term effects of the acne dosage? (100 mg 2x day) I am supposed to be on 200 twice a day but that scares me because I am so sensitive with side effects and allerigies from abx after repeat or prolonged usage.

Thanks.

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LymeEnigma
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Re: Minocycline Data

Post by LymeEnigma » Thu 7 Feb 2008 18:33

ANY idea the long term effects of the acne dosage? (100 mg 2x day) I am supposed to be on 200 twice a day but that scares me because I am so sensitive with side effects and allerigies from abx after repeat or prolonged usage.
I've often wondered how one might fare, after knocking the bacteria into submission, lowering to a "maintenance dose" of various antibiotics, as opposed to continuously blasting them ... and one's body with it. Had anyone tried anything like that?

cave76
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Re: Minocycline Data

Post by cave76 » Thu 7 Feb 2008 19:09

****I've often wondered how one might fare, after knocking the bacteria into submission, lowering to a "maintenance dose" of various antibiotics, as opposed to continuously blasting them ... and one's body with it. Had anyone tried anything like that?****

No, but I'm about to. :) Maybe. Probably.

Since I've been on abx for SO long (because I needed them)

since I'm doing better now--- no 'cure' but functioning fairly well

since I know that abx isn't probably the 'cure' but they sure make more logic than a lot of other things

since I'm not about to swallow bleach or sputniks

since I'm 'afraid' to stop them (yeah, abx seeking behavior!)

since, since, since----

Now I just have to figure out which abx to use long term. I'm considering doxy, 100 mg a day.

But, but, but.

Until something comes up that makes as much sense as long term abx---- I guess I'm stuck with them.

[The above is NOT medical advice!!! It's me thinking out loud,fer cryin' out loud.]:bonk:

Joe Ham
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Re: Minocycline Data

Post by Joe Ham » Thu 7 Feb 2008 20:08

Itsy wrote;
***I find it (and tetracycline) greatly greatly helped my narcolepsy... ***

My reaction to Mino seems to be related but opposite. After a week or so the evening dose would keep me awake for a few hours. I note that the half life is given as 16 to 20 hours so there may be some gradual build up, maybe more likely with me because my liver and kidneys are getting old.

When the insomnia gets bothersome I skip a dose and things seem to "reset". I have no idea if my low dosage regimen is subtherapeutic or not except for a hint that it might be doing some good by preventing the 3 AM angina attacks. 100 mg bid is my current dosage. When I tried it at 200 mg bid the side effects of headaches and dizziness were a problem.

Getting a handle on the 3 AM "angina" attacks is problematic. One duc called it "unstable" angina, somewhat like Prinzmetal angina. Another duc thought it was pericardial effusion. The latter seems more likely because the discomfort is mostly relieved by sitting up and leaning forward slightly, classic for effusion. However, it could be endothelial inflammation that is being suppressed by Mino. That is also possible because Mino is said to be slightly immunosuppressive. But who knows? The basic research just hasn't been done yet, or at least I haven't been able to find it.

The most frustrating aspect of all this is that the cardiac ducs around here are so myopic that they have no freaking idea how Borrelia can affect the heart. And when they are shown recent research about the issue it seems like their eyes just glaze over. Maybe it just goes right over their head because it doesn't agree with what they learned in med school 30 years ago.

I have no idea what the long term effects of Mino might be. I chose it as a first course some time ago just because it has the best BBB penetration of the Tetras. That was about three years ago when I was "Lyme stupid" but just barely smart enough to recognize the importance of brain penetration for Neuroborrelosis. There are other Lyme ABs with good BBB penetration but that discussion may be best done on another thread.

***I know narcolepsy seems to be a problem with the hypocreitian (sp?) transmitters from chronic inflammation in some part of the brain ...***

I haven't noticed anything about that but now that you have brought it up I will keep an eye open for it. Thanks for your input on this.

Joe

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