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61.
Patricia Puebla Pilar Pastoriza Emilia Barcia Ana Fernández-Carballido 《Journal of microencapsulation》2013,30(7):793-808
The aim of this study was to obtain biodegradable indomethacin microspheres for intra-articular administration in rheumatoid arthritis, where angiogenic processes are involved. Indomethacin concentrations to achieve an anti-angiogenic effect would be five-times higher than an anti-inflammatory. Microspheres were prepared by solvent evaporation using PLGA. Indomethacin is a poor water-soluble drug with it being possible that dissolved and non-dissolved drug co-exist within the polymeric matrix resulting in rapid release. To control this release, an oil-PEG-derivative was incorporated, producing changes in morphology, crystallinity and indomethacin release. To minimize the amount of microspheres administered, a two-factor five-level central rotable composite 22?+?star design was employed with two independent variables: indomethacin percentage and PEG-derivative percentage. The optimum formulation showed mean encapsulation efficiency of 94.3?±?2.2% and released 7.99?±?0.25?µg indomethacin/day/mg microspheres for 21 days. A dose of 20–50?mg of this formulation could be appropriate to achieve both anti-angiogenic and anti-inflammatory effects. Preliminary cytotoxicity studies performed in rat splenocytes showed an adequate cell viability. 相似文献
62.
《Current medical research and opinion》2013,29(1):64-65
SummaryA double-blind crossover trial of 200?mg flurbiprofen daily and 100?mg indomethacin daily, each given for 2 weeks separated by a 1-week placebo washout period, was carried out in 30 patients with rheumatoid arthritis. The results were analyzed for the 26 patients with complete records. No statistically significant differences were found between the two treatments with regard to subjective impression of pain severity, duration of morning stiffness, grip strength, joint size, haemoglobin and erythrocyte sedimentation rate. When the results for each treatment period were compared to baseline and both drugs considered individually, there was a statistically significant improvement from baseline. During the flurbiprofen treatment period the erythrocyte sedimentation rate showed a statistically significant fall, but not with indomethacin. During the placebo washout period between the active therapies, there was a statistically significant worsening in all parameters apart from the level of haemoglobin and erythrocyte sedimentation rate. These assessments showed little change. Five patients reported side-effects with indomethacin, and 1 with flurbiprofen. No side-effects were reported during the placebo period and although 4 patients were withdrawn, none was withdrawn because of side-effects. Patient preference was for flurbiprofen. 相似文献
63.
《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
64.
《Current medical research and opinion》2013,29(1):70-75
SummaryA double-blind crossover trial in 50 patients with rheumatoid arthritis was carried out to compare the clinical effectiveness of 800?mg. azapropazone per day with 100?mg. indomethacin per day. Blood plasma concentrations of azapropazone were also studied in 10 patients.Patients received both drugs for a 3-week period, the order of treatment being determined at random. Although there were no marked differences in any of the objective measurements, patients' assessments of response to and preference for each drug treatment period suggested that azapropazone produced significant improvement compared to that with indomethacin. Plasma levels of azapropazone remained remarkably constant for each patient. Side-effects with both drugs were mild and transient, and there were no marked variations from normal in any of the laboratory parameters measured. 相似文献
65.
《Current medical research and opinion》2013,29(2):158-169
SummaryIn a 6-week open study in 24 patients with rheumatoid arthritis, tolmetin was shown to have analgesic and anti-inflammatory activity at daily doses in excess of 1200 mg per day and produced statistically significant reductions in overall joint pain, walking time and articular index. The drug was well tolerated, but 2 patients were withdrawn because of persistent indigestion and 1 because of an urticarial type rash.In a double-blind crossover comparison against indomethacin and placebo in 22 patients, 1400 mg tolmetin daily showed efficacy comparable with that of 150 mg indomethacin daily. Few side-effects were reported and did not necessitate any patients being withdrawn. 相似文献
66.
《Expert opinion on pharmacotherapy》2013,14(9):1917-1928
Preterm delivery (before 37 completed weeks of gestation) is the major determinant of infant mortality. In women with a previous preterm birth associated with bacterial vaginosis, prophylactic antibiotics (e.g., metronidazole) reduce the risk of preterm birth and low birth weight. Trichomonas vaginalis increases the risk of preterm delivery, but metronidazole is not beneficial for this and may even be detrimental. Antibiotic use (e.g., erythromycin) prolongs pregnancy in late premature rupture and has health benefits for the neonate. However, antibiotics are probably not useful in preterm labour. Intramuscular 17α-progesterone and vaginal progesterone reduce the rate of preterm labour in high-risk pregnancies, including previous spontaneous preterm delivery. Magnesium sulfate, β2-adrenoceptor agonists and the oxytocin-receptor antagonist, atosiban, are effective in reducing uterine contractions short-term, but there is little evidence that this leads to improved outcomes for the neonate. However, tocolysis with calcium-channel blockers does seem to lead to better outcomes for the neonate. Fetal side effects, such as ductus arteriosus constriction and impaired renal function, are associated with the inhibition of prostaglandin synthesis with indomethacin. New approaches and more effective drugs are required in the treatment of preterm delivery. 相似文献
67.
It was reported that the plasma concentration of indomethacin was increased with concomitant oral dosages of diflunisal in humans. Both indomethacin and diflunisal are glucuronidated in humans. The effects of diflunisal on the indomethacin glucuronidation were thus investigated in vitro using human liver microsomes (HLM) and human intestine microsomes (HIM) in order to assess the drug-drug interaction. The glucuronidation of indomethacin in HLM showed atypical kinetics with Km and Ksi values of 210 and 89.5 microM, respectively, while HIM exhibited Michaelis-Menten kinetics with a Km value of 17.4 microM. Diflunisal inhibited the indomethacin glucuronidation in HLM with IC50 values ranging from 100 to 231 microM. In HIM, inhibition of the indomethacin glucuronidation by diflunisal was more potent with IC50 values of 15.2-48.7 microM. When the clinical dose of diflunisal (250 mg b.i.d.) is taken into consideration, it is expected that the diflunisal concentration in the intestine would be higher than the IC50 values for indomethacin glucuronidation in the intestine. These findings suggest that the clinical drug-drug interaction between diflunisal and indomethacin may be at least partly attributable to the inhibition of indomethacin glucuronidation by diflunisal in the intestine. 相似文献
68.
69.
大剂量酮洛芬与吲哚美辛的致小鼠胃粘膜损伤作用 总被引:2,自引:0,他引:2
目的研究大剂量酮洛芬(Ket)、吲哚美辛(Ind)致小鼠胃粘膜损伤及其与胃组织中前列腺素(PG)、氧自由基(OFR)及一氧化氮(NO)含量的关系。方法①测定小鼠胃粘膜损伤指数;②测定胃组织PGE2、MDA含量;③测定血浆、胃组织中NO含量。结果16,32mg·kg-1Ket和Ind均能引起小鼠胃粘膜损伤,Ind的致损伤作用更为显著。Ket和Ind组胃组织中PGE2、MDA含量较对照组降低,而NO含量显著增高。结论大剂量Ket、Ind可致胃粘膜损伤,且Ket引起的损伤程度较轻;胃组织内PGE2含量降低和NO含量异常增高可能是Ket和Ind致胃粘膜损伤的重要机制。 相似文献
70.
章京 《第二军医大学学报》1988,(2)
实验观察了“安全”减压和不适当减压条件下家兔减压病(DCS)的发病情况、Doppler超声以及血浆中TxB_2和6-keto-PGF_(1a)的变化;还观察了消炎痛对DCS的预防怍用。结果显示:减压愈不当,DCS发病愈重,Doppler超声气泡探测仪检测到的级别愈高。血浆TxB_2、6-keto-PGF_(1α)值在濒死动物中明显升高(P<0.01);存活动物中,TxB_2经历了下降、再恢复的过程(P<0.01),而6-keto-PGF_(1α)值未见明显变化。消炎痛在抑制血浆TxB_2升高的同时,有效地降低了DCS发病率。此结果表明:TxA_2、PGI_2参与了重型DCS的发病过程,消炎痛的顶防作用与抑制花生四烯酸代谢物的生成有关。 相似文献