Seibel Klaus, Schaffler Klaus, Reeh Peter, Reitmeir Peter
HPR - Human Pharmacodynamic Research GmbH, Munich, Germany.
Arzneimittelforschung. 2004;54(8):444-51. doi: 10.1055/s-0031-1296997.
In the treatment of painful conditions the time to onset of a drug's analgesic effect is of great relevance. Plain ibuprofen acid (Ibu, CAS 15687-27-1) is relatively slowly absorbed after oral administration (t(max) is about 90-120 min). If, however, ibuprofen is given in form of a lysine salt, absorption is much quicker. It has been shown in pharmacokinetic studies that the maximum plasma concentration after administration of an ibuprofen lysine tablet (IbuLys) is reached at about 35 min after oral administration. The aim of this study was to evaluate the onset and extent of the analgesic effect of 400 mg ibuprofen administered as marketed ibuprofen lysine tablets (two tablets of Dolormin as a single dose) in comparison with standard Ibu tablets (two tablets as a single dose) and placebo (Plc) utilising the objective, quantitative (high resolution) method of Laser algesimetry. The N1-P2 peak-to-peak amplitude of the Laser-induced somatosensory evoked potentials (LSEPs)--measured during the first two hours after administration of study drugs--was the main efficacy parameter for the onset of the analgesic effects. The values obtained during 5 h after administration of the study drugs were used to measure the extent of the analgesic effects. As a main result with respect to the onset of analgesic action, the reduction of the N1-P2 peak-to-peak amplitude was significantly and relevantly more pronounced during the first 2 h after administration of IbuLys than after Ibu (IbuLys vs. Plc: p < or = 0.0020, IbuLys vs. Ibu: p < or = 0.0366). During the same time the amplitudes of the single N1-components of the LSEPs were also significantly smaller after IbuLys than after Plc (p < or = 0.0031) whereas the difference between plain Ibu and Plc was not significant (p < or = 0.1027). As a measure of the extent of analgesic action, the N1-P2 peak-to-peak amplitudes recorded during 5 h after medication were more effectively reduced by IbuLys than by Ibu (IbuLys vs. Plc: p < or = 0.0001, IbuLys vs. Ibu: p < or = 0.0041, Ibu vs. Plc: p (0.383). The reduction of the amplitudes of the single N1-components by IbuLys was significant in comparison to Plc (p < or = 0.0031), but not in comparison to Ibu. During the time of 5 h after medication the attenuating (analgesic) effect of IbuLys on the amplitude of the P2 component of the LSEPs was stronger than that of Plc (p < or = 0.0053) and stronger than that of Ibu (p < or = 0.0058). In summary IbuLys was significantly superior to Ibu with respect to the onset and extent of the analgesic effect. drugs were used to measure the extent of the analgesic effects. superior to Ibu with respect to the onset and extent of the analgesic effect.
在疼痛病症的治疗中，药物镇痛效果的起效时间至关重要。普通布洛芬酸（Ibu，化学物质登记号15687 - 27 - 1）口服后吸收相对缓慢（达峰时间约为90 - 120分钟）。然而，如果布洛芬以赖氨酸盐的形式给药，吸收则快得多。药代动力学研究表明，口服布洛芬赖氨酸片（IbuLys）后，约在35分钟达到血浆最大浓度。本研究的目的是采用客观、定量（高分辨率）的激光痛觉测定法，评估以市售布洛芬赖氨酸片（两片多洛芬作为单剂量）形式给药400毫克布洛芬的镇痛效果的起效时间和程度，并与标准布洛芬片（两片作为单剂量）及安慰剂（Plc）进行比较。在给予研究药物后的头两小时内测量的激光诱发体感诱发电位（LSEPs）的N1 - P2峰峰值幅度，是镇痛效果起效的主要疗效参数。在给予研究药物后5小时内获得的值用于测量镇痛效果的程度。关于镇痛作用的起效，给药后前2小时内，IbuLys给药后N1 - P2峰峰值幅度的降低比Ibu给药后显著且更明显（IbuLys与Plc比较：p≤0.0020，IbuLys与Ibu比较：p≤0.0366）。在同一时间，IbuLys给药后LSEPs单个N1成分的幅度也比Plc给药后显著更小（p≤0.0031），而普通Ibu与Plc之间的差异不显著（p≤0.1027）。作为镇痛作用程度的衡量指标，给药后5小时内记录的N1 - P2峰峰值幅度被IbuLys比Ibu更有效地降低（IbuLys与Plc比较：p≤0.0001，IbuLys与Ibu比较：p≤0.0041，Ibu与Plc比较：p 0.383）。与Plc相比，IbuLys使单个N1成分幅度降低具有显著性（p≤0.0031），但与Ibu相比则不然。在给药后5小时内，IbuLys对LSEPs的P2成分幅度的衰减（镇痛）作用比Plc更强（p≤0.0053）且比Ibu更强（p≤0.0058）。总之，在镇痛效果的起效时间和程度方面，IbuLys显著优于Ibu。使用药物来测量镇痛效果的程度。在镇痛效果的起效时间和程度方面优于Ibu。
