Prednisone, Lodotra, and Circadian Rhythm

Hi arvine. You can purchase Lodotra from northdrugstore.com. Their phone number is 1-866-940-3784 and they are in Toronto.

You can also copy and paste the following into your search bar:

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The revealing chart on page 5 shows the plasma concentrations of Decortin (Predisone) vs. Rayos (Lodotra). This makes it obvious that half of the anti-inflammatory effect of either drug is gone in about 5 hours and quickly diminishes thereafter. For this reason, as PMRpro pointed out, timing can be very important.

The release profile of these drugs was designed to match the peak release of natural cortisol in the body, which corresponds with our 24 hour circadian rhythm. Please look at figure 1 in the following document:

ncbi.nlm.nih.gov/pmc/articl...

From this you will better understand the body's natural rhythm and understand the reason for the drug's short half-life. When tapering, it is believed that timing the drug, (which peaks in approximately 2 hours) with this natural circadian rhythm helps the HPA axis (your body's adrenal system) to start producing cortisol once again. .

17 Replies

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  • I have always understood the timing with Rayos/Lodotra to be nothing to do with the corticosteroid release in the body but the shedding of the cytokines that cause the inflammation in the body - by releasing the pred at 2am, the peak is at 4am or so and deals with the pro-inflammatory cytokines at source so to speak. That is confirmed/mentioned a few times in the document for which you provided the link, one occasion being at the top of page 10. The circadian rhythm in question is not that of the adrenal glands secretion of cortisol but that of the body shedding pro-inflammatory cytokines:

    "The progression of RA and other inflammatory diseases is characterized by a circadian

    rhythm of pro-inflammatory cytokines. This often results in particularly severe signs and symptoms of disease in the morning hours. Patients with active RA suffer from clinical signs and symptoms that include joint stiffness, pain, and swelling. Clinical symptoms vary during the day and are more severe early in the morning after awakening than in the afternoon or evening. Indeed, morning stiffness is a prominent symptom of RA." (page 2)

    The graph you refer to is merely to show the time lag when Rayos' special modified release coating encloses prednisone and then breaks in half after 4 hours in the right conditions - they are both for the same active substance, prednisone, not different drugs.

    Even with Lodotra there is still adrenal suppression - it doesn't make a lot of difference when you take it if you are on much more than 10mg, there will be suppression - and the same slow reduction is still needed to recover normal adrenal function.

    The other paper you cite appears to be about modified release hydrocortisone which has a very short halflife and so is classed as a short-acting corticosteroid - with a short duration of effect that means for managing PMR it would be dosed twice daily at least. That is why it isn't generally used for PMR - pred is a medium acting corticosteroid with a longer halflife and duration of effect of 12-36 hours making it ideal for once daily dosing which has the effect of improving compliance.

  • That is interesting what you say about adrenal suppression and Lodotra. I have got down to 5mg and have been waiting for the fatigue of the adrenal glands waking up and it has not happened yet for some unknown reason. Perhaps I am such a couch potato I would not notice any extra fatigue!

  • I was fine at 5mg, 4mg I was still pretty good. 3.5mg - felt as if I had been hit by a ton of bricks!

  • I will wait and see!

  • All became theoretical in February - but I'm alternating 7 and 8mg ...

  • Any fatigue at that dose?

  • Could sleep for Britain given half a chance. But fatigue, no.

  • I wonder if Lodotra does make a difference. That would be interesting.

  • What - to fatigue?

  • The adrenal fatigue.

  • Dunno - we can do a study...

  • I will let you know if I get hit by a truck at 3mg too.

  • PMR Pro, I used the first link to demonstrate the short half life of prednisone and the necessity of timing it with the shedding of inflammatory cytokines.

    The second citation (which is regrettably not working as I write) demonstrated the breakfast cortisol secretory episode, a mid-morning snack episode, a lunch episode, a mid-afternoon snack episode, a supper episode, and a late snack episode. The first and largest breakfast episode is the one Predisone's short half-life was designed to emulate.

    Regrettably I have not found a way to copy and paste charts and other graphics to my reply and therefore used a citation which was apparently subject to the vagaries of the internet.

  • The second isn't about pred - it's about hydrocortisone. I did read it.

  • The following may be easier for you to understand, but you will note the acrophase lines on figure 1 match the more smoothed lines on the Wilson Chart.

    pathways4health.org/2009/11...

    Merry Christmas

  • Please don't patronise me - I do have a physiology degree and have worked in medical/pharmacology fields for many years!

    The second paper is about delayed release hydrocortisone for replacement therapy in adrenal insufficiency. The clue is in the title:

    "Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy"

    There is no link between adrenal sufficiency and the management of PMR. At least, not until you get to the lower doses of pred after a protracted period of higher dose corticosteroid - and then the link is still nothing to do with the management of the PMR.

  • In my post I wrote the following: "The release profile of these drugs was designed to match the peak release of natural cortisol in the body, which corresponds with our 24 hour circadian rhythm. Please look at figure 1 in the following document:

    ncbi.nlm.nih.gov/pmc/articl...

    From this you will better understand the body's natural rhythm and understand the reason for the drug's short half-life. When tapering, it is believed that timing the drug, (which peaks in approximately 2 hours) with this natural circadian rhythm helps the HPA axis (your body's adrenal system) to start producing cortisol once again:"

    Note the words "Look at the chart". This diagram was used only to demonstrate circadian rhythm of cortisol, which can be clearly seen and is labeled as follows: " Circadian rhythm of cortisol in 33 individuals with 20-minute cortisol profiling".

    The chart which shows the release profile of prednione and Lodotra was prefaced with the following statement: The revealing chart on page 5 shows the plasma concentrations of Decortin (Predisone) vs. Rayos (Lodotra). This makes it obvious that half of the anti-inflammatory effect of either drug is gone in about 5 hours and quickly diminishes thereafter. For this reason, as PMRpro pointed out, timing can be very important.

    Once again it was meant to demonstrate the short half-life of pred, the importance of timing, and its similarity to the major breakfast circadian cortisol peak.

    As for education, I have a BS in industrial engineering as well as biomedical engineering and when I worked in the medical field, I Installed and trained lab personnel on the following instruments: Corning LARC Automatic White Cell Differential Classifier, Adac Gamma Counter, Leitz Immunofluorescent microscope, Coulter Blood Cell Counter, Hycel Multi-Channel Blood Chemistry Analyzer, Perfusion Coagulation Tester, Coleman spectrophotometer, Sciex Capillary Electrophoresis, and the Megaquant Stat Chemistry Analyzer.

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