theophylline absorption

don't think increased temperature should make a difference. Any gut symptoms (diarrhoea etc) cos they can reduce absorption. I suppose a change in diet could too - are you eating lots of cranberries? or any new drugs including herbals?

Can't think of any other reasons it shoudl have been so low.

s

i haven't had any more gut probs than usual (i have ibs) and i wouldn't say my diet has been any different as i have so many allergies i have to be very careful about what i have so i've been cooking everything myself.

Becky I take 1400mg a day and can STILL have a level below 1 !!

I just have a very short half life - get rid of it to quick !!

Cons dont know why but I am not the only one at our clinic either !!

Hi Becky,

I have the same problem, I am on 400mg eight hourly and my levels can range from normal to very low. I'm very sensitive to any drop in levels and will almost certainly splatt if it goes too low.

As you say there are lots of things that can affect the metabolism including drugs and change in diet or alcohol intake. In my case though I think it's not a metabolism problem but an absorption problem - like you I have IBS and when I get a flare-up of it I do tend to drop my theophylline levels. I was switched to taking it eight hourly rather than 12 hourly for that reason and it does seem to have helped a bit.

The problem is that if it is an absorption problem it will be likely to be variable and erratic and therefore just putting up the dose is no good cos some of the time you would end up toxic.

This topic has been discussed at great length in the past, it's one of the recurrent topics on here, so you might want to check out the old threads for any other ideas.

Sorry, I don't think there are any easy answers!

Get well soon

Em H

thanks emily, that's helpful. the doc i saw yesterday indicated he thought it might be an absorption thing rather than an increase in metabolic rate and elimiation of theo, but also seemed to be guessing.

how do i go about checking old threads on this topic?

Hi Becky,

I've brought the thread to the top that had the most lengthy discussion of theophylline levels... it's pretty long, happy reading!

Take care,

Em H

thanks for that emily, that made vey intersting reading and i could relate to a lot of it. i have been extremely toxic in the past to the extent where i was having major tonic-clonic convulsions (that i don't remember but was told about) that they were sure were going to leave me at least with severe brain damage if i survived at all. i thnk they said the longest fit i had was about 45 mins with very little relief with diazamuls. however, i lived to tell the tale and thankfully with no long-term results (did have fits for a while afterwards though not now and not diagnosed as epileptic either). still, it's made me nervous about getting toxic again in the future. however that's kind of the opposite to where i've been at this time with a level of 1.2

I would suggest your cons at home does absorbtion tests. They are pain but worth it as it can narrow down if it is metbolism, absorbtion or simply just your liver clearing it like mad. Basically they give supervise you having your normal dose (to rule out non-complience) and then do blood tests every hour, if you are lucky they can get the blood through a canula or if not like me you go and get bleed hourly. They can see from the way your levels change over the 8 hours how you are absorbing it etc, from there that can try and work out a dose and regime. it is extremly rare for them not to be able to sort out your levels either by juggling the dose or helping your digestive tract to absorb it.

If you take stupid amounts IV to get you to thereputic and you don't smoke (which I know you don't) then odds apparently are it is super liver problem not how it absorbs through the digestive tract and might be resolved simply by upping the dose a little.

One other thing how long after you had taken your last dose did they do the test? It should be within 4-6 hours but if you were rushed in and bloods done say 10 hours after your last dose that might would explain it.

I hope that makes sense I have been reading up on this recently and have 1st hand experience too!

Bex

owner of one of the most super livers around

i just remembered that i did a pubmed search on this earlier and after a lot of huntig came across one litle bit of potentially interesting info. according to the abstract of this article written in 1991 'theophylline clearance was found to be increased by ... terbutaline ... - typically by 25 per cent but sometimes as much as 80 per cent ...' whilst i don't take terbutaline as such my cons said that bambuterol is converted into terbutaline in the body. i wonder if this could be a contibutory factor to this splat ... though it doesn't quite fit because i've now been on bambuterol for almost 7 weeks so i'd havethought that if this were the reason then it'd have happened wll before now. i thought others might be intersted too though.

Do you have link for this I am going to show it to clinical cons at the RBH. Mind you my levels were pants before the terbutaline sub cut.

Bex

I have just been remined by eldest of the time I was admitted to Torbay and my levels where ""trace"" after a frustrating 10 minutes where I was accused of not taking my meds, we worked out I was due to take my phylocontin before being abducted and by the time they took the blood etc I was almost 12 hours from last dose. This was in the pre 8 hourly days but does show how fast it drops out of the system,

Bex

Thats interesting becky a si was on terbu when my last lot of levels were 7 despit being on 1250mg per day. Would like the link as well!! Good research mate!!

i do't have the link but i took down the referenc info - clin. pharmacokinet. 1991 jan 20 (1): 66-80 'pharmacokinetic interactions between theophylline and other medications (part 1)', by Upton, R. A.

you'll find it on pubmed.com

it doesn't take stupid amounts of iv amino to get me therapeutic, just the usual 0.5ml/kg usually but it takes several hours for it to kick in. it was probably getting on for about 10 hours since my previous dose so that may well be the explanation for such low levels but i wouldn't have thoughtitd have bee that low and it hasn't to my knowledge been that low i the past ... unless i just haven't been told.

I think this talks about it but my brain is mush mode findarticles.com/p/articles... will deffo mention to the RBH when next there althogh it seems to say in artical I found that salbutamol also increased clearence.

bex

They normally do regular tests between 4-6 hours from taking your dose (some drs say 4 hours some say 6) which is why your levels when on routine check might be OK. The time mine were ""trace"" were back when I was on 450mg phylocontin bd since moving to 8 hrly doses I don't think the problem as been as bad mind you I am on a lot more phlyocontin now. although my levels are always low they are more consistently low over the day if you see what I mean.

Bex

edited to correct 500 to 450

Regarding the timing of the test, I was always told that it's done as a 'trough' level, ie just before you're due to take the next dose, which sort of makes sense given that the aim is to be therapeutic throughout the whole twelve hour period.

The way the tablets are designed, (the slow release formulation) they are *supposed* (in normal people!) to give fairly steady levels throughout the twelve hour period. I recently had pre- and post-dose levels done, to try to unpick the whole low levels problem, and both times when I had them done the two levels were almost identical, which puzzled me at the time until one of the pharmacists pointed out that that is exactly what the tablets are meant to do!

I always get good levels on the standard IV dose of aminophylline, which is what makes me think that it's an absorption issue with my IBS: not to go into too much detail, but if the tablet isn't staying in your gut for 12 hours then you will not stay therapeutic for 12 hours!

Wish there was an easier answer to this cos when my levels are good theo is my wonder drug!

Take care all

Em H

Emily H - I've always had 'trough' readings done too as it picks up what amount is left in your system.

When on IV if at strong dose I get good levels but as soon back onto sr tabs they go way down.

When I was on normal release Nuelin liquid (now withdrawn) I was on what the cons termed a 'legal overdose' as was on twice sometimes triple the max dose BUT because it was taken 4 times a day it kept my levels up.

None of the local resp cons will put sr tabs up to a more frequent level due the toxicity risks.

One thing I found that really lowered my levels once on IV was giving up caffeine - caffeine pushes levels up 'in some people' but when I gave it up levels plummeted.

Now I just have what caffeine I want but I'm seriously interested in the Terbutline side mentioned as I take - Bricanyl normal release tablets (15mg a day) and a very high dose of the Bricanyl respules.

I take 800mg Uniphyllin in the morning and 600mg at night and my levels are often low when they are tested on admission. I have been accused several times of not taking it which really annoys me. Do they really believe that I would deliberately make myself worse by skipping my medicine.

It responds to IV Aminophylline and picks up again but when I'm back on the tablets it goes down.

no reason for it but they reckon I must metabolize it very quickly as the dose I am on could make other people very unwell.

Me too Karly, have just had two weeks iv aminoph and during this was only theraputic for two days and as soon as stop and on just oral has plumeted too my boots again!!! whats that all about, yet they wont increase my oral dose incase get toxic!!! as if!!! one pharmacist acussed me of smoking as this decreases levels i was like yeah and that would be possible with my lungs and on oxygen!!! bint!!!

Love

Andrea xxx

Well guys I just want to buck the trend here my level 11 on 675 bd and 12.9 on 450 am and 675 pm- confirms my belief that there is absolutely no rhyme or reason to this at all both taken 6 hrs post morning dose.

Work that one out!

Den

As I understand it and I have done a bit of reserch into this some people don't correctly absorb amino via tablets and there are things they can do. If you take a high doses of tablets are a non smoker and you get thereuputic on your average amounts of amino IV (roughly 1 - 1.5 grams over 24 hours) the odds are you fall into this not absorbing bracket it is by far and away the more common one, sadly it seems that all too often it is not investigated and people have to trundle along when it is possible something could be done.

If you take stupid amounts by tablet and need stupid amounts IV ( eg 2.5 grams over 24 hours) to get thereuputic then you are in trouble as you metabolise it too well and there really is not much they can do about it.

It is worth esp is you fall into the 1st set of people and frankly just to prove you take the damned things if you fall into the 2nd one requesting asborbtion studies. You take your normal dose infront of medics to prove you have taken it they do bloods for theo level every hour for 8 hours and they can see the pattern and decide if there is something they can do to help you aborb it, or maybe move you to a 3 times a day regime etc.

I am told the metabolism (needs stupid amounts IV and via tablet) is very rare. I am the only person I know who needs as much amino as I do and who clears it as fast as I do, within hours (as proved by the absorbtion studies). I know of one other person who can tolerate IV amino at above the 2.5 but in their case it seems this tops them up. In my case take it down and within hours it is gone. I never even on vast amounts of tablets get close to thereuputic, As for being toxic you are having a laugh even on the highest doses of IV amino my top level was 14. There is a plus side to all this I must have an amazing liver and consider it my medical duty to challenge it with G&T on a regular basis

Bex

Poor absorption vs rapid metabolism

Thanks Bex, I was going to say that!

Poor absorption can be for a variety of reasons (in my case irritable bowel and rapid GI transit time I think), the tablet is designed to stay in the gut for 12 hours gradually releasing the drug, and if it is not in the gut for 12 hours, or if part of the gut is not absorbing properly, there will be trouble. If you have a rapid transit time there are drugs that can slow it, such as codeine or loperamide. If you are also skinny and/or anaemic, it's worth asking about gut diseases such as coeliac or inflammatory bowel disease which could cause an area of the gut to become diseased and not absorb properly. If you have this problem, it can be helped by taking the theophylline in 3 doses 8 hours apart, which is what I do. In the old days there used to be a non-slow release syrup which could be taken up to 6 times a day, which would be a hassle but would get round most of the absorption problems.

My problem is that I appear to absorb it in a variable and erratic way depending on what my bowels are doing, so the dose I need one day might send me toxic the next day! Figures.

If you absorb it alright but are possessed of the best liver in the Northern hemisphere (showoff! ) then your enzymes will be metabolising it as quickly as, and often there is not a lot to be done. In theory stupid doses could be prescribed orally but it's a dangerous game cos liver activity can vary and without having levels checked virtually daily there would be a risk of severe toxicity (and for those who haven't had the pleasure, mild toxicity is really not fun!). Occasionally there is a reason for the super enzymes such as smoking or being on another drug which induces the enzymes (phenytoin, carbamazepine, barbituates, rifampicin, chronic excess alcohol). If this is stopped then the enzymes eventually go back to normal. There is a preparation, Phyllocontin Forte, which is designed for smokers and those with rapid metabolism and a decreased half-life, but I'm not sure it differs except being a higher dose.

Of course the flip side to this is that there are also a lot of drugs which inhibit the action of the enzymes and can potentially make the theophylline levels go toxic - hopefully no-one's GP would prescribe something which would seriously interact (these days 'computer says no' if you try to do anything like that!) but the list bears repeating. The main ones are antibiotics like erythromycin, ciprofloxacin, metronidazole, isoniazid and chloramphenicol; the anti-stomach acid drugs omeprazole and cimetidine; heart drug amiodarone; gout drug allopurinol; thrush treatment ketoconazole; acute alcohol intoxication. There are many others, but these are the main ones. That's not to say that if you're on theophyllines you should never have these drugs, but certainly if you have a short course the levels should perhaps be monitored. If you are started on any of these long-term then you will perhaps need to reduce the dose of theophylline. Of course, you should discuss it with your doctor. There are also foods which can interact, though this is rarely enough to have any clincal effect.

When I was a student, my theophylline dose was increased, and shortly after that I noticed that I was getting horrendous hangovers all of a sudden. Nausea, constant vomiting, pounding headache, racing heart etc, much worse than anything I'd ever experienced before. I even ended up in A&E with dehydration once because I couldn't keep fluids down, which was embarrassing! After three or four of these (I'm nothing if not persistent!) I realised that what was happening was that the acute alcohol intake was inhibiting my enzymes and causing theophylline toxicity. The problem was easily remedied by only taking half a tablet at night on the days when I'd been out on the town. (NOTE: I am NOT recommending this as a strategy, it's a really good way to get a) seriously toxic if you drink a lot and don't reduce the dose enough; or b) subtherapeutic and with worsening asthma if you reduce too much. Only fiddle with the dose with the advice of your doctor or asthma nurse! And don't binge drink! Okay, rant over.) If you do drink a lot at irregular times and notice this though, at least you now know what's going on.

Well, I seem to have written a pharmacology essay, so I'll stop now before I get drummed out of AUK for being terminally boring.

Take care all

Em H

EmilyH, terminally boring I soooooooooo don't think so. TY for putting my somewhat rambling explaination into sensible speak!

S'not my fault I have a super liver, I am an organ doner so although my crappy lungs won't be worth anything I like to think so someone suddenly getting a turbo charged liver after I shuffle off the mortal coil (but not fora long time yet).

Bex

I hear these days they can divide the liver and give it to two people, I'm sure yours though will do at least ten, Bex!

Bex what I gained from the Emily's post was that drinking can up ammo levels and you could try that in order to get theraputic those g+t might really be of some use.

Den

Unfortunately Den, although drinking acutely (ie infrequent binges) inhibits your enzymes and raises your theo levels, drinking regularly actually induces your enzymes and lowers your levels!

Although probably not significantly unless you are putting away an awful lot more than the odd G & T!

OK Den and Emily, just sort it out how many G&T's can I have per day

Bex

Well, you could always try a bottle of gin a day to try and give yourself cirrhosis, that would reduce those enzyme levels of yours! Although knowing your liver you'd probably need more than a bottle a day.

Or you could try not drinking regularly and just having the occasional binge to get your levels up for a particular special occasion... trouble is all your special occasions would have to be endured with a hangover.

Ooooh I am such a bad doctor suggesting such things!

Yeh Bex now you know what to do - shove the iv ammo top ups to get levels up just go on a bender once every few days and it should work nicely.

Den

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