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  • Title: Plasma levels after peroral and topical ibuprofen and effects upon low pH-induced cutaneous and muscle pain.
    Author: Steen AE, Reeh PW, Geisslinger G, Steen KH.
    Journal: Eur J Pain; 2000; 4(2):195-209. PubMed ID: 10957700.
    Abstract:
    Cutaneous applications are gaining popularity in the treatment of cutaneous pain and of painful disorders in joints and muscle. The low pH-pain model in human skin has previously been able to demonstrate the effects of NSAIDs in dose-dependent manner and to establish time-effect relationships. We examined the analgesic action of ibuprofen after cutaneous application and compared the effects with oral administration. The two studies (with n = 12 subjects each) were performed in a double-blind, randomized fashion with a 1-week cross-over interval. In study 1 volunteers received intradermal infusions with phosphate buffered saline solution of pH 5.2 and received either 800 mg ibuprofen per os and topical placebo, or 4 g of a 5% commercial ibuprofen gel topically applied and oral placebo capsules, respectively. In study 2 the same protocol was applied with painful intramuscular infusion of stronger, isotonic phosphate buffer (pH 5.2). The flow rate of the pH-infusion was individually adjusted to induce pain with a magnitude of 20% on a visual analogue scale (ranging from 'no' (0%) to 'unbearable pain' (100%)). Ibuprofen (S-, R-) plasma levels after oral administrations were measured with HPLC, and after topical applications, by gas chromatography combined with mass spectroscopy to determine plasma levels in the range of ng/ml. In the cutaneous model pain ratings decreased to zero after topical verum gel within 45 min of the observation period of 55 min. Pain reduction after peroral ibuprofen was of the same magnitude, but was achieved within only 30 min. In the muscle model, the commercial ibuprofen gel did not reduce the pain in the acidic muscle. The peroral ibuprofen was less effective in the muscle compared to the skin pain model, although there was a significant progressive pain reduction within 55 min. Reasons for the differential susceptibility of cutaneous vs muscular acidosis pain to ibuprofen remain to be established.
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