Plasma levels after peroral and topical ibuprofen and effects upon low pH‐induced cutaneous and muscle pain

European Journal of Pain - Tập 4 Số 2 - Trang 195-209 - 2000
Astrid Steen1, Peter W. Reeh2, Gerd Geißlinger3, Kay H. Steen4
1Klinik und Poliklinik für Dermatologie der Universität Bonn, Klinische Dermatophysiologie, Sigmund-Freud-Str. 25, Bonn, D-53105, Germany
2Institut für Physiologie und Experimentelle Pathophysiologie, Universität Erlangen-Nürnberg, Universitätsstraße 17,D-91054 Erlangen,Germany
3Institut für Klinische und Experimentelle Pharmakologie und Toxikologie, Universität Erlangen‐Nürnberg, Universitätsstraße 22, D‐91054 Erlangen, Germany
4Klinik und Poliklinik für Dermatologie der Universität Bonn, Klinische Dermatophysiologie, Sigmund‐Freud‐Str. 25, D‐53105 Bonn, Germany

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

Baillie T.A., 1989, Mechanistic studies of the metabolic chiral inversion of R‐ibuprofen in humans, J Pharmacol Exp Ther, 249, 517

10.1111/j.1572-0241.1999.01087.x

Berner G., 1989, Percutaneous ibuprofen therapy with Trauma‐Dolgit gel: bioequivalence studies, Drugs Exp Clin Res, 15, 559

10.1016/S0304-3959(98)00062-1

Dominkus M., 1996, Comparison of tissue and plasma levels of ibuprofen after oral and topical administration, Arzneimittelforschung, 46, 1138

10.1007/BF01990960

10.1007/BF03258452

Giese U., 1990, Absorption and distribution of ibuprofen from a cream formulation after dermal administration to guinea pigs, Arzneimittelforschung, 40, 84

Günther S., 1999, Rises in [Ca2+]imediate capsaicin‐ and proton‐induced heat sensitization of rat primary nociceptive neurons, Eur J Neurosci, 11, 3141

10.1007/BF00583640

10.1016/0304-3940(96)12576-3

10.1016/0304-3959(92)90262-A

10.1016/0304-3959(94)00265-G

Longhurst J.C., 1991, Ischemically sensitive abdominal visceral afferents: response to cyclooxygenase blockade, Am J Physiol, 261, H2075

10.1016/S0304-3959(96)03316-7

10.1016/S0009-9236(98)90150-3

10.1002/cpt1969102213

10.1080/00140139308967931

Steen A.E., 1998, Effects of peroral and topical ibuprofen upon low pH‐induced cutaneous and muscle pain, Pflügers Arch, 435, R152

Steen A. E., 1996, Topical acetylsalicylic acid applied to the skin of herpes zoster‐patients strongly reduces their acute neuralgia, R276

Steen K.H., 1998, Sustained acidosis induces sensitization to heat stimulation of rat cutaneous nociceptors, in vitro. Pflügers Arch, 435, R152

10.1016/0304-3940(95)12002-L

10.1523/JNEUROSCI.12-01-00086.1992

10.1016/0304-3959(95)00087-9

10.1016/0304-3959(95)00011-G

10.1016/0304-3959(96)03034-5

10.1163/092996397750131892

10.2165/00003495-199856050-00004

Wegner H., 2000, Neurosci Lett

Thông tin
Thông tin xuất bản

European Journal of Pain

Tập 4 Số 2

195-209

Thông tin tác giả