Any reasonable explanation for why ibuprofen doesn't work but both celebrex and meloxicam do (beside

I’ve got pain in my legs of indeterminate cause and 800mg ibuprofen does nothing at all - I’d almost think it makes it worse. The other day I tried 200 mg celebrex and was surprised it worked. The next day I tried 15mg meloxicam and that also worked. My understanding is that these are all cox inhibitors with only slight differences in mechanisms of action. Does it not make sense that one wouldnt work at all why the other 2 would? I’ve read on pubmed that those are all roughly equivalent dosages. Thanks.

Last time I looked into why different NSAIDs work differently on different people, there was still no good solid idea as to the reason. I suspect as we learn more about different genotypes of folks, we’ll get more clues as to the reason, and eventually we’ll prescribe a specific NSAID for pain relief based on a person’s DNA analysis.

Meanwhile most of us practitioners use trial and error. I like to start out with meloxicam or naproxen as they are longer acting, but eventually will try all 5 different classes of Cox-I inhibitors to see if any one works better for a particular patient. I don’t tend to use Cox-II meds because despite claims as to their superiority in not causing GI problems, the evidence shows they cause just as much GI bleeding as COX-I. Also they’re much more expensive.

In my household, I use naproxen when I have acute pain of great severity. Meanwhile the Mrs. states naproxen does absolutely nothing for her, and goes to either ibuprofen or diclofenac.

Medical advice is best suited to IMHO.

General Questions Moderator

I wasn’t seeking medical advice. Perhaps I didn’t make it clear but I was looking for explanations about their differing mechanisms of action. I would prefer this be treated as a GQ. I’m seeking facts not opinion.

Ok so I’m not crazy. I hate to think my body is not being rational. :wink:

I concur, the observation that different NSAIDs work differently for different people (and even differently for the same folks at different times) is definitely a question medical scientists are trying to answer. I do hope someone does stop by with more current info.

There may be some mechanism-of-action subtleties related to which COX is being inhibited preferentially by which drug, but there are plenty of other parameters which also need to be considered.

Absorption and distribution of particular drugs can vary widely between individuals, as can rate of metabolism. Each of these can affect how much of the drug is present at the site of injury (or whatever) to provide pain relief. If you’re a poor absorber or fast metaboliser of ibuprofen (say), that might be a factor.

Off the top of my head I can’t remember if the different NSAIDS are metabolised by the same species - I’ll take a look if I have the chance.


This chart:

  • lists the isoforms of CYP450 which are responsible for the metabolism of numerous analgesics.

Amongst the NSAIDS mentioned in this thread, metabolism is by

Ibuprofen: 2C9, 2C19
Meloxicam: 2C9, 3A4
Naproxen: 1A2, 2C9
Diclofenac: 2C9, 3A4

  • so there are some differences in how the drugs are metabolised. IANA Biochemist but I know that not everyone produces the same isoforms, at least not to the same extent, so it may be that different individuals metabolise NDAIDs at different rates depending on their production of the metabolic agents specific to each NSAID.

Regarding absorption of the drug in the first place, this is best described by something called the Biopharmaceutics Classification System (BCS) classification of the individual drugs, but I haven’t found a handy tabulation for NSAIDs yet.

Is this helping? Or do you already have more than you want?


The celebrex also works for me with my leg pain. The ibuprofen also helps but not nearly as effective. I only use the celebrex if the pain gets extreme as I am a little afraid of the side effects. Also I find the celebrex to be therapeutic and not just a pain reliever. Very often I have taken 1 pill and it seems to resolve the issue for a while.

I’ll chime in that Advil always helps for cramps but Aleve does - nothing - and ditto the occasional headache.

I’ll weigh in that only Aleve works for headache/muscular pain/toothache for me.

And I’ll just note that advil and aleve are ibuprofen and naproxen, respectively.

Even within the same individual, might not different drugs have different effectiveness vs. different kinds of pain? Like, someone might find that drug 1 works better than drug 2 for leg cramps, but the reverse for sinus headaches.

Sure. I find aspirin oddly effective for headaches, but for muscle/joint aches I find ibuprofen much more effective, and naproxen less effective than ibuprofen, but much more effective than aspirin.

Actually naproxen works about as well as ibuprofen, except I need to take twice the “standard” dose to get the same effect, whereas I take the recommended dose of ibuprofen. I’ve often wondered why it is that I need to double the dose for naproxen.

My ex-husband was prescribed naproxen for migraines before it became OTC and the dosage was 500mg. Aleve tabs are 220mg so two of those fairly closely approximates the original dosage from when it was script only. That’s what I take when I use it–I’m on warfarin so NSAIDs are a very seldom thing for me. I’d take meloxicam if I could because of the longer effective period for a smaller dosage but it not only fights with warfarin but also with the ACE inhibitor I take for blood pressure. So that’s a “no” for me.

I’m not aware of any special concerns for meloxicam about ACE inhibitors, other than the general precaution about ACEI use with NSAIDs, and I just checked UpToDate on the topic. Can you elaborate on that? Of course being on warfarin makes any NSAID use relatively contra-indicated.

I always check WebMD or the like before asking my doc about a possible medication change, and a couple different sites said there’s a problem mixing meloxicam and Lisinopril (which is what I take) with no specific reason as to why it’s not good, but I asked my doc if it’s okay and he said he wouldn’t recommend the combination. So I dropped it, it’s not like my occasional use of naproxen is problematical anyway–I was just researching possible alternatives if my pain phase of frozen shoulder turned out to be more protracted than my tolerance of chronic pain. It’s going into “still frozen but nowhere near as painful” territory so the point’s moot anyway.

I dug a little deeper into the issue of meloxicam and lisinopril, and didn’t find much more of significance, other than there may be a bit of a theoretical concern that chronic use of meloxicam and lisinopril together could be slightly riskier that using other NSAIDs chronically with lisinopril. My sources didn’t feel there was a real significant problem with episodic use of meloxicam (or any other NSAID) and lisinopril.

But do what works for you.

I tend to err on the side of caution regarding meds and interactions–I’ve known not a few people who had some big conflicts that never got caught before they caused some fairly hairy symptoms. I’m probably more paranoid than need be, but the warfarin thing is nothing to fuck around with–people think I’m scared of bleeding out when what really concerns me is getting into a car accident and dying (or ending up dain bramaged) from ICP before anyone figures out there’s a problem. That’s my nightmare, in case anyone’s keeping track. :wink:

Another anecdote: About 9 years back, I developed fairly severe knee pain pretty much out of the blue. They’ve always tended to random ouchiness but this took it to a whole new level. Ibuprofen did little.

Then the doc gave me Arthrotec (an overpriced combination of diclofenac and misoprostol; both available as generics but putting them together let the drug company charge brand-name prices).

And that worked like a DREAM. The misoprostol was to protect the stomach from the diclofenac; it may well have done so but it also gave me farts-from-hell :D.

I told my doctor it was her fault that I sprained my ankle: because I was feeling so much better, I was walking too fast, turned my ankle, and went down like a sack of potatoes.

Any NSAID works far better for me than Tylenol (acetominophen or paracetamol). I had surgery that same year for something else, and the 10+ days beforehand when I couldn’t take any NSAIDS really sucked. And this year when I had wrist surgery, I was very relieve when doc said I could take NSAIDs, as the Percocet (Tylenol + narcotic) was NOT doing a good job.