I. Tegeder et al., Application of microdialysis for the determination of muscle and subcutaneous tissue concentrations after oral and topical ibuprofen administration, CLIN PHARM, 65(4), 1999, pp. 357-368
Background: The topical administration of non-steroidal antiinflammatory dr
ugs (NSAIDs) is widely used for the treatment of soft tissue pain. However,
it is not known whether effective tissue concentrations are reached with t
he topical route.
Objective: To evaluate and compare unbound muscle and subcutaneous tissue i
buprofen concentrations with use of microdialysis after topical and oral ad
Methods: In a 2-way crossover design, 11 healthy volunteers received either
800 mg oral ibuprofen or 16 g of 5% ibuprofen gel applied onto the skin of
the thigh (defined area, 17 x 19 cm). Microdialysis catheters were inserte
d into the medial vastus muscle (25 to 30 mm) and into the subcutaneous adi
pose layer of the thigh (4 to 5 mm), Dialysate was collected in 20-minute i
ntervals up to 5 hours.
Results: Essentially all of the orally administered dose was recovered in u
rine as ibuprofen or metabolites during 24 hours, but only about 0.55% of t
he topically administered dose was recovered. The relative systemic bioavai
lability of ibuprofen gel, based on urine recovery data, was (mean +/- SD)
0.57% +/- 0.30%. Mean values of the dialysate areas under the drug concentr
ation-time curves after topical and oral administration were 731.2 +/- 605.
0 and 176.6 +/- 122.9 ng.h.mL(-1) for subcutaneous tissue and 63.5 +/- 90.3
and 213.4 +/- 117.2 ng.h.mL(-1) for muscle, respectively. Muscle dialysate
concentrations after topical administration varied considerably among the
Conclusion: These results suggest that, if target tissue concentrations cor
relate directly with the degree of pain relief, patients with pain caused b
y dermal or subcutaneous tissue damage will have greater pain relief after
topical administration of ibuprofen accompanied with less systemic side eff
ects. In addition, a proportion of patients with muscle pain may also exper
ience pain relief from topical ibuprofen.