Guest guest Posted January 6, 2004 Report Share Posted January 6, 2004 a and Terri, I took a stab at this question, and, try as I might, I couldn't keep my answer short, LOL. I don't know what reference Terri's PCP used to come to this conclusion, but I'm pretty sure it's based on Enbrel's plasma half-life (there are other types of half-life measures, but I will limit this discussion to plasma half-life). Maybe you could ask your PCP how he/she came to the conclusion that Enbrel remains in the body for 10-12 weeks, Terri? From everything I've read and VERY generally speaking, biologics like Enbrel (etanercept) are thought to be quite biodegradable and cleared by the body fairly easily. We don't have to worry about them lingering in the tissues and recirculating for extremely long periods of time like, for example, the non-biologic Arava (leflunomide) does. Even though Arava's half-life is around 2 weeks, it may persist in the body for up to 2 years! That's an advantage if it's working well and not causing other problems, but a very serious issue if toxicity occurs - hence, the washout procedure available that is recommended for those who must discontinue Arava. How long a drug remains in the body depends on the drug's properties, half-life being one of the most important of them, and the person receiving the drug. Everyone's own particular circumstances - state of health, other medications, individual make-up, and so forth - will influence how long the drug will remain in the body. For this discussion, I'll assume that Enbrel's half-life is the most important factor. I'm also going to make one more assumption: we're talking about someone who has reached a steady-state plasma concentration of Enbrel. By definition, the plasma half-life is the amount of time it takes for only half of the original amount of a drug to remain in the plasma. That is, after one half-life, 50% of the drug is eliminated from the plasma, 50% is left. After the next half-life (the 2nd one), half of the remaining 50% (25% of the original amount) is lost (75% of what was there originally is now gone). After 3 half-lives, 12.5% more is lost (87.5% of the drug is gone). After 4 half-lives, 6.25% more is lost (93.75% of the drug is gone). After 5 half-lives, 3.125% more is lost (96.875% of the drug is gone). After 6 half-lives, 1.563% more is lost (98.438% of the drug is gone). After 7 half-lives, 0.781% more is lost (99.219% of the drug is gone). So, as a practical example, let's say you've been on Enbrel for awhile and you give yourself a 25 mg injection on the 1st of January. We'll assume that the entire 25 mg is available in the plasma to begin with (and we'll disregard whatever is left from previous injections so we can keep things simple). After the 1st half-life, 12.5 mg is left. After the 2nd half-life, 6.25 mg is left. After the 3rd half-life, 3.125 mg is left. After the 4th half-life, 1.563 mg is left. After the 5th half-life, 0.781 mg is left. After the 6th half-life, 0.391 mg is left. After the 7th half-life, 0.195 mg is left. But how long is each half-life? If you read the manufacturer's findings from the clinical trials (and the link a gave has this information: http://www.rxlist.com/cgi/generic/etanercept_cp.htm), the half-life is given as: " median half-life of 115 hours (range 98 to 300 hours " ). That's an average of about 4.8 days. So, on average, you would be expected to lose 50% of the amount of Enbrel available at the beginning of the half-life cycle every 4.8 days. 1 half-life = 4.8 days 2 half-lives = 9.6 days 3 half-lives = 14.4 days 4 half-lives = 19.2 days 5 half-lives = 24.0 days 6 half-lives = 28.8 days 7 half-lives = 33.6 days So, in around 33.6 days (7 half-lives), on about February 3rd, you would have about 0.195 mg of the 25 mg of Enbrel you injected on January 1st left in your plasma. Even at the 4th half-life you only have 1.56 mg left and that would be only January 20th. Keep in mind that we are only talking about that one injection and, in reality, the prior injections would contribute to the total amount of Enbrel in the body also. What if you are one of those people listed in that range of half-lives from the study data provided by the manufacturer and your half-life is 300 hours (longer and more problematic if you wish to discontinue Enbrel for an infection)? That means each half-life cycle is 12.5 days. The 4th half-life is at 50 days, the 5th half-life is at 62.5 days, the 6th half-life is at 75 days (10.7 weeks), and the 7th half-life occurs after 87.5 days or 12.5 weeks. Maybe the 6th and 7th half-life cycles in this example is where Terri's doctor drew the conclusion that Enbrel remains in one's system for 10 - 12 weeks (which is the worst-case scenario according to the study data). Other sources list Enbrel's half-life as an average of 70 hours, so, if that's true, we would have a half-life cycle of 2.9 days. The 4th half-life would occur at 11.6 days, the 5th at 14.5 days, the 6th at 17.4 days, and the 7th at 20.3 days. So, for a half-life of 70 hours, Enbrel would leave your system very quickly after you stopped taking it. Even if you have some of the Enbrel left in your body, just how much is enough to cause trouble should you have an infection? I don't know, but I'm guessing that by the time you are at the 4th half life of the last injection you took and beyond, the small amount left in your body shouldn't be a problem. Enbrel doesn't stop you from producing TNF (which is a cytokine key to fighting infection), rather it binds to TNF available in circulation and reduces TNF activity. The less Enbrel you have left, the less it is able to interfere with TNF. And, theoretically, those with RA are making more TNF than the average person. Re: [ ] Enbrel > Terri, > I've looked and can't find anything that says Enbrel stays in the body for > 10-12 weeks. I'll keep looking. Maybe what your doctor is referring to > is the 2-5 time increase in serum levels after taking Enbrel over time. > > http://www.rxlist.com/cgi/generic/etanercept_cp.htm > > Half life of medications is defined as the amount of time it takes the body > to eliminate half of the drug after it has been absorbed by the body. > Even though Enbrel has a short half-life, it may still accumulate even > though most of it leaves the body. This is probably why the serum levels > are 2-5 times higher in people taking Enbrel over time. I'm not sure if the > levels that build up leave us more susceptible to infection. You know I'll > be looking for the answer to that question. I hope you don't have any more > trouble with diverticulitis. My mom had it several years ago and it was > very painful. > > > Some articles on biologicals and infection: > > Enbrel has a median half-life of about 115 hours whereas Remicade's > elimination half-life is 8.0-9.5 days. This was taken from this article: > > Etanercept, Infliximab, and Infection: > http://216.239.41.104/search?q=cache:91IgXHME6GEJ:www.mgh.harvard.edu/id/hms > /handouts20012002/infliximab.pdf+enbrel+remicade+half-life & hl=en & ie=UTF- 8 > > Here is a Medscape article that discusses the various half-lives of > biologicals: > " Infliximab is a chimeric (human/mouse) anti-TNF monoclonal antibody with a > half-life of 8-10 days; etanercept is a fusion protein of the TNF receptor > and the immunoglobulin G (IgG)-Fc-region, with a half-life of 4 days. The > first is administered every 4-8 weeks intravenously; the second is > self-administered weekly subcutaneously. " > http://www.medscape.com/viewarticle/459048 > > a > > > > > > When I was on Enbrel the first time around and had a bad infection > > (diverticulitis) my pcp looked up and studied Enbrel and it was found to > > stay in the body about 10-12 weeks the same amount of time that it takes to > > build up in the body. > > > > Terri Quote Link to comment Share on other sites More sharing options...
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