Glucosamine synergistic with ibuprofen

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Jan 15, 2002

Glucosamine synergistic with ibuprofen

Philadelphia, PA - Glucosamine, the nutritional supplement widely used by

osteoarthritis patients, has demonstrated a synergistic effect with

ibuprofen, showing enhanced pain relief in an experimental model. The

researchers are now planning to test the combination of glucosamine and

ibuprofen in a clinical trial to determine whether the same effect is seen

in patients: it may allow lower doses of ibuprofen to be used, with a

resultant reduction in the risk of side effects.

In the same model, glucosamine demonstrated no analgesic activity when used

on its own. But when it was used in combination with ibuprofen, the pain

relief obtained was 2 to 3 times greater than that seen with ibuprofen

alone, one of the researchers, Dr Alan Cowan (Temple University School of

Medicine, Philadelphia, PA), tells rheumawire.

The researchers also tested several other nonsteroidal anti-inflammatory

drugs (NSAIDs). The combination of glucosamine with naproxen, indomethacin,

piroxicam, and diclofenac all produced an additive effectbut because the

analgesic effect of glucosamine alone was zero, in practice the combination

with glucosamine with these drugs produced the same analgesic effect as the

NSAID used alone, Cowan explains. However, the combination of glucosamine

with aspirin and with acetaminophen (paracetamol) was subtractivethe pain

relief obtained was less than with aspirin or acetaminophen alone.

" It's a big jump from this mouse model . . . to patients with osteoarthritis

who are taking these drugs every day for a long time, and there is still a

lot more research that needs to be done. "

This work, reported in the Journal of Pharmacology and Experimental

Therapeutics [1], was carried out in a standard pain model, the mouse

abdominal irritant test. " It's a big jump from this mouse model, which tests

an acute dose of the drug, to patients with osteoarthritis who are taking

these drugs every day for a long time, and there is still a lot more

research that needs to be done, " Cowan cautions, but he feels there are

clinical implications from the research. The synergy exhibited by the

glucosamine and ibuprofen combination was striking, and the mouse work

strongly suggests that the combination is more potent than the individual

components, he comments. As both products are well known and widely used,

rheumatologists can recommend to their osteoarthritis patients that they try

the combination, and by adding glucosamine to ibuprofen, patients may be may

be able to reduce the dose of the anti-inflammatory, he says.

Work is now under way at Temple to formulate a combination product of

glucosamine with ibuprofen, with patents already filed. It's an area in

which these researchers already have some experience: the 2 other authors on

the paper, Dr Tallarida and Dr Raffa (Temple University School

of Medicine), were both involved in the development of Ultracet®

(Ortho-McNeil Pharmaceutical Inc, Raritan, NJ), a combination of tramadol

with acetaminophen, which is used in osteoarthritis. " Combining pain

relievers into 1 pill can increase patient compliance, simplify prescribing,

and improve efficacy without increasing side effects or, conversely,

decrease side effects without losing efficacy, " they comment.

" Like finding buried treasure . . . "

In the paper, the researchers comment that the statistically significant

synergy seen with glucosamine and ibuprofen (and also with glucosamine and

ketoprofen) stood out " in stark contrast " to the additive or subtractive

interactions seen with the other products. They add that actual evidence of

synergy (analgesia statistically greater than the expected additivity) has

rarely been documented. Discovering it is " like finding buried treasure, "

Tallarida comments in a press release issued by the university.

The synergism was shown to depend strongly on the proportions of the agents

in the combination, thereby emphasizing that a synergistic interaction is

not merely a property of the constituentsit also depends on their relative

proportions. Cowan told rheumawire that the best effect was seen when

glucosamine and ibuprofen were used in a ratio of 9:1.

The researchers homed in on ibuprofen for further study because the product

is so widely used. An investigation of pharmacokinetics showed that the

answer doesn't lie thereit's not a case of the presence of glucosamine

increasing the concentration of ibuprofen in the blood. But a preliminary

exploration of the 2 enantiomers (R and S) of ibuprofen revealed that the 2

differ both in terms of their analgesic effect and pharmacological

properties (the R-enantiomer doesn't inhibit cyclooxygenase), providing a

hint that synergy may be achieved by some mechanism that doesn't involve COX

inhibition. Further investigations are now in progress. Cowan says that this

work in itself is rather exciting, as it may be that 1 of the isomers in

itself could be used therapeutically, either alone or in combination with

ibuprofen.

The finding that glucosamine on its own did not block pain (even at the

highest dose, 500 mg/kg) confirms what has been suspected for some timethat

the supplement does not have intrinsic analgesic activity. From a reading of

the literature, Cowan says his understanding is that the pain relief that is

reported by patients using glucosamine appears to stem from its

disease-modifying effects and its effects on cartilage and bone.

Zosia Chustecka

Source

1. Tallarida RJ, Cowan A, Raffa RB. Antinociceptive synergy, additivity, and

subadditivity with combinations of oral glucosamine plus nonopioid

analgesics in mice. J Pharmacol Exp Ther 2003 Nov; 307(2):699-704.