title: Pharmacokinetics and bioavailability of percutaneous ibuprofen.
abstract: The absorption, pharmacokinetics and bioavailability of ibuprofen (CAS 15687-27-1) were investigated for an ibuprofen gel preparation (ibugel) for percutaneous application, and compared to a standard oral ibuprofen tablet preparation. The monocentric, randomised, 2-way cross-over study with 7-day wash-out period was performed on 18 healthy female volunteers with an average age of 26.3 +/- 4.8 years (range: 20-38 years), average weight 60.4 +/- 7.6 kg, and average height 164.7 +/- 5.9 cm. Blood samples were taken from the volunteers before administration of the tablet or gel, and periodically during 24 h after administration. The ibuprofen content in these samples was determined using a validated HPLC method. Main pharmacokinetic parameters derived from individual plasma concentration-time courses included: Cmax, tmax, AUCO-->24, AUCO-->infinity, MRTO-->infinity, t1/2 and Frel. For percutaneous application of 500 mg ibuprofen (10 g 5% gel on the back, area of 20 x 20 cm) with occlusion for 2 h, a Cmax of 7.1 +/- 4.4 micrograms/ml (95% confidence interval (CI): 5.0-9.1) was obtained at 2.4 +/- 0.8 h (95% CI: 2.0-2.8). For oral administration of 400 mg, Cmax was 36.7 +/- 7.5 micrograms/ml (95% CI: 33.2-40.1) at 1.1 +/- 0.8 h (95% CI: 0.7-1.5). The (dose-corrected) relative bioavailability of the topical ibuprofen was found to be 22 +/- 12% (95% CI: 14-30%) of that after oral administration. The plasma elimination half-life was 2.5 +/- 1.4 h (95% CI: 1.9-3.2) for topical administration, and 1.8 +/- 0.5 h (95% CI: 1.6-2.1) after oral administration (not significant, p > 0.05). The surprisingly high levels of ibuprofen found in the plasma after percutaneous application are still below the threshold where systemic side effects might be expected (10 micrograms/ml). The high peak plasma concentration and relative bioavailability of percutaneous ibuprofen are likely due to the galenical formation of the gel preparation, which contains isopropyl alcohol and propylene glycol as co-solvents and is adjusted to pH 5, and to the use of occlusion.
authors.affiliation: Clin-Pharma Research Ltd., Birsfelden, Switzerland.
authors.forename: C H
authors.initials: CH
authors.lastname: Kleinbloesem
authors.forename: M
authors.initials: M
authors.lastname: Ouwerkerk
authors.forename: W
authors.initials: W
authors.lastname: Spitznagel
authors.forename: F E
authors.initials: FE
authors.lastname: Wilkinson
authors.forename: R R
authors.initials: RR
authors.lastname: Kaiser
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005079:Excipients; D005260:Female; D005782:Gels; D006207:Half-Life; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D005782:Gels; D013607:Tablets; D007052:Ibuprofen