Comparison of two different preparations of ibuprofen with regard to the time course of their analgesic effect. A randomised, placebo-controlled, double-blind cross-over study using laser somatosensory evoked potentials obtained from UW-irritated skin in healthy volunteers.
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.
Seibel
Klaus
K
HPR - Human Pharmacodynamic Research GmbH, Munich, Germany. HPR.Pharmacodynamics@t-online.de
Schaffler
Klaus
K
Reeh
Peter
P
Reitmeir
Peter
P
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007834:Lasers; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D018401:Sample Size; D012867:Skin; D014466:Ultraviolet Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen