Application of microdialysis for the determination of muscle and subcutaneous tissue concentrations after oral and topical ibuprofen administration

Citation
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
Citations number
76
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN journal
0009-9236 → ACNP
Volume
65
Issue
4
Year of publication
1999
Pages
357 - 368
Database
ISI
SICI code
0009-9236(199904)65:4<357:AOMFTD>2.0.ZU;2-J
Abstract
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 ministration. 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 subjects. 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.