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1.
Werner Neupert Roland Brugger Christian Euchenhofer Kay Brune Gerd Geisslinger 《British journal of pharmacology》1997,122(3):487-492
- Ibuprofen enantiomers and their respective coenzyme A thioesters were tested in human platelets and blood monocytes to determine their selectivity and potency as inhibitors of cyclo-oxygenase activity of prostaglandin endoperoxide synthase-1 (PGHS-1) and PGHS-2.
- Human blood from volunteers was drawn and allowed to clot at 37°C for 1 h in the presence of increasing concentrations of the test compounds (R-ibuprofen, S-ibuprofen, R-ibuprofenoyl-CoA, S-ibuprofenoyl-CoA, NS-398). Immunoreactive (ir) thromboxane B2 (TXB2) concentrations in serum were determined by a specific EIA assay as an index of the cyclo-oxygenase activity of platelet PGHS-1.
- Heparin-treated blood from the same donors was incubated at 37°C for 24 h with the same concentrations of the test compounds in the presence of lipopolysaccharide (LPS, 10 μg ml−1). The contribution of PGHS-1 was suppressed by pretreatment of the volunteers with aspirin (500 mg; 48 h before venepuncture). As a measure of LPS induced PGHS-2 activity immunoreactive prostaglandin E2 (irPGE2) plasma concentrations were determined by a specific EIA assay.
- S-ibuprofen inhibited the activity of PGHS-1 (IC50 2.1 μM) and PGHS-2 (IC50 1.6 μM) equally. R-ibuprofen inhibited PGHS-1 (IC50 34.9) less potently than S-ibuprofen and showed no inhibition of PGHS-2 up to 250 μM. By contrast R-ibuprofenoyl-CoA thioester inhibited PGE2 production from LPS-stimulated monocytes almost two orders of magnitude more potently than the generation of TXB2 (IC50 5.6 vs 219 μM).
- Western blotting of PGHS-2 after LPS induction of blood monocytes showed a concentration-dependent inhibition of PGHS-2 protein expression by ibuprofenoyl-CoA thioesters.
- These data confirm that S-ibuprofen represents the active entity in the racemate with respect to cyclo-oxygenase activity. More importantly the data suggest a contribution of the R-enantiomer to therapeutic effects not only by chiral inversion to S-ibuprofen but also via inhibition of induction of PGHS-2 mediated by R-ibuprofenoyl-CoA thioester.
- The data may explain why racemic ibuprofen is ranked as one of the safest non-steroidal anti-inflammatory drugs (NSAIDs) so far determined in epidemiological studies.
2.
目的 评价布洛芬软胶囊治疗偏头痛急性发作的疗效和安全性。方法 随机、双盲、安慰剂交叉对照的多中心临床试验。共入组偏头痛病例120例,实际完成病例数为111例,其中先服布洛芬后服安慰剂组55例;先服安慰剂后服布洛芬组56例。治疗前两组的一般资料、临床评价和实验室指标无显著性差异。结果 布洛芬组和安慰剂组2小时内头痛消失率分别为(48.65±4.74)%和(19.82±3.78)%(P<0.01)。布洛芬组和安慰剂组2小时内头痛缓解率分别为(79.28±3.85)%和(45.05±4.72)%(P<0.01)。结论 布洛芬治疗偏头痛安全性好,可作为治疗偏头痛急性发作的有效药物。 相似文献
3.
Flurbiprofen, like its predecessor ibuprofen, possesses antipyretic properties in the endotoxin-fevered rabbit. Comparison of flurbiprofen and ibuprofen at varying dosages, reveals that flurbiprofen is at least 15 times more potent in this species. In goats, flurbiprofen is more potent than in rabbits. Flurbiprofen inhibited the pyrogenic effect of intravenously administered leucocytic pyrogen, but it did not alter the release of leucocytic pyrogen from peritoneal exudate cells in vitro. Moreover, flurbiprofen did not inhibit endotoxin-induced release of endogenous pyrogen in vivo. Incubation of leucocytic pyrogen with flurbiprofen did not alter its pyrogenic poteny. These results suggest that the antipyretic activity of flurbiprofen is due neither to interference with endogenous pyrogen synthesis and release, nor to inactivation of circulating endogenous pyrogen. 相似文献
4.
目的与布洛芬缓释胶囊对照,评价大骨节Ⅰ号方胶囊治疗大骨节病的疗效。方法选择大骨节病患者210例随机分为治疗组105例、对照组105例,分别予口服大骨节Ⅰ号方胶囊、布洛芬缓释胶囊。各组服用3个月后观察疗效,同时观察停药半年、1年的疗效。结果3个月后,两组的疗效差异无统计学意义(P〉0.05),但治愈率、不良反应率差异有统计学意义(P〈0.01或P〈0.05);停药半年、1年的随访观察中两组临床疗效、治愈率差异有统计学意义(P〈0.01或P〈0.05)。结论大骨节Ⅰ号方胶囊治疗大骨节病的治愈率、不良反应率及远期疗效优于布洛芬缓释胶囊。 相似文献
5.
《Current medical research and opinion》2013,29(8):542-546
SummaryA trial was carried out to assess the value of ibuprofen in relieving the symptoms and signs in 40 patients suffering from inflammatory phlebopathies of the lower limbs. Ibuprofen was given in a dosage of 900?mg. daily for periods ranging from 7 to 28 days. Spontaneous pain, redness and oedema showed a marked reduction, on average by the third day, although pain on pressure persisted for about 10 days. Body temperature returned to normal within a few hours. The results were assessed as excellent in 10, good in 19,fair in 8, and poor in 3 patients. Side-effects were reported inonly 3 patients and were mild. 相似文献
6.
《Current medical research and opinion》2013,29(8):513-515
SummaryA study was carried out to determine the effects of ibuprofen, phenylbutazone and indomethacin at different concentrations on phytohaemagglutinin-induced stimulation of lymphocytes in vitro. The results indicate that all three drugs inhibit lymphocyte stimulation, and at concentrations achieved by ibuprofen and phenylbutazone in vivo. It may be, therefore, that part of the effect of ibuprofen in rheumatoid arthritis is due to inhibition of lymphocyte function. 相似文献
7.
《Current medical research and opinion》2013,29(8):791-799
SUMMARYObjective: The objective of the two pharmacokinetic studies reported here was to compare the relative bioavailability of an ibuprofen/pseudoephedrine modified-release capsule with each of the active ingredients given alone as standard formulations.Study design: Evaluation of two open, randomised, cross-over studies, one single dose and one multiple dose, in healthy male volunteers.Methods: Healthy volunteers were randomised in a cross-over design to single or multiple doses of a combination of ibuprofen (600 mg) plus pseudoephedrine (90 mg) in a slow-release formulation and the individual active products alone as standard formulations; ibuprofen 400mg, pseudoephedrine 60 mg.Results: The single-dose study demonstrated that the bioavailabilities of ibuprofen and pseudoephedrine achieved with the slow-release formulation were not significantly different from those with standard tablets of each ingredient alone. In addition, mean plasma levels of ibuprofen predictive of clinical efficacy were achieved within 0.5-1 h and lasted for 10-12 h thereafter. The time required to reach clinically effective blood levels of pseudoephedrine was longer, starting at approximately 2 h. However, the plasma levels predicted that the clinical effect would then last for at least a further 12 h. Trough levels from the multiple-dose study showed that clinically relevant analgesic and decongestant plasma levels were maintained for 24 h during twice-daily dosing. The slow-release formulation was well tolerated with only mild adverse events.Conclusion: Blood levels would predict that the present slow-release fo rmulation of ibuprofen plus pseudoephedrine should offer reliable day and night control of cold and flu and sinus symptoms and be associated with a favourable safety profile. 相似文献
8.
《Current medical research and opinion》2013,29(8):522-524
SummaryThirty patients with chronic rheumatic conditions and a known history of peptic ulceration were treated with ibuprofen, 600?mg. to 1200?mg. daily. Six patients withdrew from the study. In the remaining 24 patients, ibuprofen gave effective relief of symptoms and did not aggravate the gastro-intestinal pathology. 相似文献
9.
10.
《Current medical research and opinion》2013,29(8):525-527
SummaryA comparative open study was made of the effectiveness of four antirheumatic agents in the treatment of 69 hospitalised patients with rheumatic diseases who had failed to respond satisfactorily to previous therapies. Simple subjective and objective assessments showed that approximately half the patients treated with ibuprofen, oxyphen-butazone or mefenamic acid showed improvement, but that fewer did so with flufenamic acid. Full therapeutic effect of the drugs was evident in approximately 3 weeks. 相似文献