Analgesic Efficacy of an Acetaminophen/Ibuprofen Fixed-dose Combination in Moderate to Severe Postoperative Dental Pain: A Randomized,Double-blind,Parallel-group,Placebo-controlled Trial

Purpose

Acute pain is a significant burden to the individual and to society. There is a clear need for a pain medication that provides improved analgesia over common analgesics, without compromising tolerability. The goal of this study was to determine the efficacy of a new fixed-dose combination of acetaminophen 975 mg and ibuprofen 292.5 mg (FDC 975/292.5) relative to acetaminophen or ibuprofen monotherapy, or placebo.

布洛芬对偏头痛大鼠模型三叉神经节神经元电压门控型钙通道的影响

目的:探讨布洛芬对偏头痛大鼠模型三叉神经节神经元高电压激活钙通道电流(HVA-ICa)的调控作用。方法:雄性SD大鼠24只随机分为3组:生理盐水(NS)组、致炎剂(IS)+降钙素基因相关肽(CGRP)(IS+CGRP)组和布洛芬组,各8只。采用新型IS构建偏头痛大鼠模型,全细胞式膜片钳技术记录急性分离的三叉神经节神经元钙电流(HVA-ICa)。结果:与NS组相比较,(IS+CGRP)组HVA-ICa峰值密度增高,激活电压向超级化方向移动(P0.05);与(IS+CGRP)组相比,布洛芬组钙电流峰电流降低(P0.05)。与NS组相比,(IS+CGRP)组半数激活电压向超级化方向移动(P0.05);与(IS+CGRP)组相比,布洛芬组半数激活电压向去级化方向移动(P0.05)。与NS组相比,(IS+CGRP)组半数失活电压向去级化方向移动(P0.05);与(IS+CGRP)组相比,布洛芬组半数失活电压向超级化方向移动(P0.05)。结论:布洛芬能够降低三叉神经节神经元HVA-ICa的幅度、促进HVA-ICa的失活。     

Randomized controlled study of telcagepant plus Ibuprofen or acetaminophen in migraine

(Headache 2011;51:533‐543) Objective.— To evaluate the efficacy and tolerability of telcagepant when co‐administered with ibuprofen or acetaminophen for the acute treatment of migraine. Background.— Telcagepant is an oral calcitonin gene‐related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. Combining telcagepant with analgesics that have a different mechanism of action could produce greater efficacy. Methods.— Randomized, double‐blind, placebo‐controlled study. Patients were randomized to treat a moderate or severe migraine headache with either telcagepant 280 mg + ibuprofen 400 mg (N = 171), telcagepant 280 mg + acetaminophen 1000 mg (N = 171), telcagepant 280 mg (N = 170), or placebo (N = 171). The primary efficacy endpoint was 2‐hour pain freedom. The study had approximately 88% power to detect an additive effect of at least 15 percentage points (telcagepant combination vs telcagepant monotherapy) and 48% power to detect an additive effect of at least 10 percentage points. Safety and tolerability were assessed by adverse events and laboratory tests. Results.— The percentages of patients with 2‐hour pain freedom were greater in each active treatment group compared to placebo (P < .001): telcagepant + ibuprofen = 35.2%, telcagepant + acetaminophen = 38.3%, telcagepant = 31.2%, placebo = 10.9%. No significant differences were seen for either of the combination groups vs telcagepant monotherapy, but both were numerically larger than telcagepant monotherapy. All the active treatments were generally well tolerated. The percentage of patients reporting any adverse event within 48 hours was higher in the active treatment groups than placebo: telcagepant + ibuprofen = 30.3%, telcagepant + acetaminophen = 31.6%, telcagepant = 24.8%, placebo = 18.2%. The most common adverse events reported by ≥4 patients in one or more of the treatment groups that included telcagepant were fatigue, nausea, dizziness, somnolence, dry mouth, and tremor. Conclusions.— The combination of telcagepant 280 mg with either ibuprofen 400 mg or acetaminophen 1000 mg did not show a statistically significant difference from telcagepant alone. Numerically greater treatment effects in the combination treatment groups over the telcagepant 280 mg monotherapy suggest that telcagepant combination treatments may merit further evaluation in studies powered to detect smaller additive benefits. (Clinicaltrials.gov; NCT00758836).     

反相离子对色谱法测定复方中右美沙芬、布洛芬含量

目的：测定复方中右美沙芬、布洛分的含量。方法：采用反相ＨＰＬＣ,以Ｓｈｉｍ－ｐａｃｋ ＣＬＤ－ＯＤＳ柱为色谱柱,乙腈－水（６５：３５,含０．００７ｍｏｌ．Ｌ＾－１ＳＤＳ,０．００７ｍｏｌ．Ｌ＾－１硝酸铵,用冰醋酸调ｐＨ至３．４）为流动相,对乙酰氨基酚为内标,于２７０ｎｍ波长处测定。结果：右美沙芬在０．０２～０．１０ｍｇ．;ｍｌ＾－１范围内呈线性关系,平均回收率为９９．２％,ＲＳＤ＝１．１％;布洛芬     

布洛芬-去甲丹皮酚偶合物的制备及其稳定性评价

目的制备布洛芬-去甲丹皮酚偶合物（IB-RP）,并考察其稳定性。方法碳酰亚胺法制备IB-RP,利用红外光谱、核磁共振和质谱对其进行结构表征,高效液相色谱法考察不同pH环境和大鼠血浆对其稳定性的影响。结果结构表征结果显示成功制备IB-RP,偶合物稳定性在高温条件下发生降解,随着pH值的上升其降解速度呈明显上升的趋势。另外,偶合物在血浆中迅速发生降解,其半衰期约为3 min。结论建立制备IB-RP的方法,其稳定性受pH值的影响,血浆中可迅速降解。     

布洛芬缓释胶囊释放介质处理方式研究

目的考察释放介质处理方式对布洛芬缓释胶囊释放度的影响。方法对不同生产企业的三批布洛芬缓释胶囊,考察了煮沸、超声、减压抽滤三种不同脱气方式对释放度的影响;对煮沸法配制释放介质,考察了放置时间对释放度的影响。结果释放介质脱气方式和放置时间,对布洛芬缓释胶囊释放度有较大影响。结论布洛芬缓释胶囊释放度检查,释放介质应使用煮沸法脱气,快速降温。     

Do nizatidine and cimetidine interact with ibuprofen?

Summary The potential for interaction between ibuprofen and two histamine H₂-receptor blocking drugs — nizatidine and cimetidine — was investigated in six healthy male volunteers aged 20 to 25 years. Each subject received placebo, nizatidine 300 mg and cimetidine 800 mg orally at 9.00 p.m. daily for six doses in three randomised treatment periods separated by eight days. On the third day of each treatment period ibuprofen 400 mg was administered at the same time and venous blood samples were taken at intervals throughout the night and subsequently up to 84 h after administration.There was no difference in the area under the plasma concentration-time curve, rate of absorption or half-life of elimination of ibuprofen between the three treatments. The elimination half-life of ibuprofen on placebo was 2.04 h. The elimination half-life of nizatidine on ibuprofen was 1.72 h and that of cimetidine was 3.54 h. The latter is higher than previously reported in normal subjects.It is concluded that neither H₂-blocker affects the kinetics of ibuprofen in man.     

布洛芬丁香酚酯微乳的镇痛作用及大鼠体内药动学研究

目的:研究布洛芬丁香酚酯微乳剂的镇痛作用及其在大鼠体内的药动学.方法:采用小鼠热板法考察布洛芬丁香酚酯微乳的镇痛作用.大鼠尾静脉给药后,分别于给药后5,10,25,40 min和1,1.5,2,3,4,5,7和9 h取血.采用高效液相色谱法测定血浆中布洛芬的浓度.结果:布洛芬丁香酚酯微乳可剂量依赖性延长小鼠热板痛阀时间,且效果等同于同剂量布洛芬.布洛芬丁香酚酯微乳及布洛芬溶液组静脉注射后的消除半衰期(t1/2)分别为(6.30±0.56)和(2.79±0.29)h,清除率(CL)分别为(94.93±12.09)和(112.17±7.00)mL·h-1·kg-1,稳态表观分布容积(Vss)分别为(543.62±64.68)和(243.12±6.87)mL·kg-1,两组存在显著性统计学差异(P＜0.05).结论:布洛芬丁香酚酯微乳与布洛芬溶液剂镇痛作用相当,静脉注射后消除时间较布洛芬明显延长.     

A randomized,double-blind crossover trial of paracetamol 1000 mg four times daily vs ibuprofen 600 mg: effect on swelling and other postoperative events after third molar surgery

AIMS: To evaluate the effect of a 3-day regimen of ibuprofen 600 mg x 4 on acute postoperative swelling and pain and other inflammatory events after third molar surgery compared with a traditional regimen of paracetamol 1000 mg x 4. METHODS: A controlled, randomized, double-blind, cross-over study where 36 patients (26 females, 10 males) with mean age 23 (range 19-27) years acted as their own controls. All patients were subjected to surgical removal of bilateral third molars. After one operation the patients received tablets of ibuprofen 600 mg x 4 for 3 days. After the other operation they received an identical regimen of paracetamol 1000 mg tablets. Swelling was objectively measured (mm) with a standardized face bow and the patients scored their pain intensity (PI) on a 100-mm visual analogue scale. RESULTS: There was no statistically significant difference between paracetamol and ibuprofen treatment with respect to effect on acute postoperative swelling. Swelling after paracetamol on the third postoperative day was 1.8% less than that after ibuprofen. Mean (95% CI) difference between treatments was -0.3 (-4.7, 4.1) mm. On the sixth postoperative day swelling after ibuprofen was 2.3% less than that after paracetamol. Mean (95% CI) between treatments was 0.2 (-2.4, 2.8) mm. There was no statistically significant difference in pain intensity between the paracetamol and the ibuprofen regimen on the day of surgery. The mean (95% CI) difference between the treatments for summed pain intensity on the day of surgery (SUMPI 3.5-11) was 3.31 (-47.7, 54.3) mm. Two patients developed fibrinolysis of the blood clot (dry socket) after receiving ibuprofen while none did this after paracetamol treatment. There was no noticeable difference between treatments with respect to appearance of haematomas/ecchymoses or adverse effects which all were classified as mild to moderate. CONCLUSIONS: A 3-day regimen of ibuprofen 600 mg x 4 daily does not offer any clinical advantages compared with a traditional paracetamol regimen 1000 mg x 4 daily with respect to alleviation of acute postoperative swelling and pain after third molar surgery.