Kleinbloesem C H, Ouwerkerk M, Spitznagel W, Wilkinson F E, Kaiser R R
Clin-Pharma Research Ltd., Birsfelden, Switzerland.
Arzneimittelforschung. 1995 Oct;45(10):1117-21.
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.
对一种用于经皮给药的布洛芬凝胶制剂（ibugel）（布洛芬，CAS 15687 - 27 - 1）的吸收、药代动力学和生物利用度进行了研究，并与标准口服布洛芬片剂制剂进行比较。在18名平均年龄为26.3±4.8岁（范围：20 - 38岁）、平均体重60.4±7.6 kg、平均身高164.7±5.9 cm的健康女性志愿者中进行了单中心、随机、双向交叉研究，洗脱期为7天。在服用片剂或凝胶前以及给药后24小时内定期采集志愿者的血样。使用经过验证的高效液相色谱法测定这些样品中的布洛芬含量。从个体血浆浓度 - 时间过程得出的主要药代动力学参数包括：Cmax、tmax、AUCO→24、AUCO→∞、MRTO→∞、t1/2和Frel。对于经皮应用500 mg布洛芬（背部涂抹10 g 5%凝胶，面积为20×20 cm）并封闭2小时，在2.4±0.8小时（95%置信区间（CI）：2.0 - 2.8）时获得的Cmax为7.1±4.4微克/毫升（95% CI：5.0 - 9.1）。对于口服400 mg，在1.1±0.8小时（95% CI：0.7 - 1.5）时Cmax为36.7±7.5微克/毫升（95% CI：33.2 - 40.1）。发现局部用布洛芬的（剂量校正）相对生物利用度为口服给药后生物利用度的22±12%（95% CI：14 - 30%）。局部给药时血浆消除半衰期为2.5±1.4小时（95% CI：1.9 - 3.2），口服给药后为1.8±0.5小时（95% CI：1.6 - 2.1）（无显著差异，p＞0.05）。经皮给药后血浆中发现的布洛芬水平出奇地高，但仍低于可能预期出现全身副作用的阈值（10微克/毫升）。经皮布洛芬的高血浆峰浓度和相对生物利用度可能归因于凝胶制剂的药剂学组成，该制剂含有异丙醇和丙二醇作为助溶剂且pH值调节为5，以及封闭的使用。
