Comparative analgesic efficacy and tolerability of ketorolac tromethamine and glafenine in patients with post-operative pain

Summary

In a randomized, single-dose, double-blind, parallel comparative trial of analgesic efficacy, 96 adult patients received either 10?mg ketorolac tromethamine or 400?mg glafenine orally the morning after surgery if they requested pain relief medication. Each patient provided a baseline pain assessment and then received the assigned medication. Patients assessed pain intensity and pain relief and reported any adverse events in interviews held 30 minutes after drug administration and then hourly for 6 hours. The demographic characteristics, baseline pain intensity, and surgical categories of the 47 patients who received ketorolac tromethamine and the 49 who received glafenine were similar. Both drugs provided prompt, sustained pain relief throughout the 6-hour observation period, and there were no statistically significant differences between the two groups in any of the efficacy measures analyzed. The global assessment recorded by patients suggested a slight clinical advantage for ketorolac tromethamine (32.6% of ‘excellent’ responses) as compared to glafenine (12.5% ‘excellent’). The differences in overall response were statistically significant (p = 0.017). Fourteen (30%) patients who received ketorolac tromethamine and 17 (35%) who received glafenine reported adverse experiences that began or seemed to worsen after administration of the study drugs. The most prominent were drowsiness and sleeping, both of which are common in post-surgical patients.     

Biodegradable microspheres of ketorolac tromethamine for parenteral administration

Ketorolac tromethamine loaded microspheres were prepared using two different polyesters, namely poly (lactic acid) and poly (glycolic acid) by solvent evaporation technique. The morphology of microspheres was analysed by scanning electron microscopy. In vitro release profiles of these microspheres were studied in phosphate buffered saline pH 7.4. The release kinetics of ketorolac tromethamine from the microspheres was evaluated by fitting the release data to the zero-order, Higuchi and korsemeyer-peppas equations. All microspheres showed initial burst release, followed by fickian diffusion of drug through microspheres. These microspheres were formulated as parenterals to have controlled release system.     

Preoperative ketorolac has a preemptive effect for postoperative third molar surgical pain

There is uncertainty regarding the role of preemptive analgesia in preventing postoperative pain. Most previous studies were of parallel design completed under general anesthesia with many confounding inter-patient's variables. The present study evaluated the efficacy of preemptive ketorolac in a crossover design in patients undergoing bilateral mandibular third molar surgery. This was a double blind, randomized, placebo-controlled study where 34 patients had each of their identical impacted mandibular third molars removed under local anesthesia on two occasions. Each patients acted as their own control; one side was pretreated with intravenous ketorolac 30 mg before surgery followed by placebo injection after surgery, and for the other side, the patient was given placebo injection before surgery and post-treated with intravenous ketorolac 30 mg after surgery. The difference in postoperative pain between pretreated and post-treated side in each patient was assessed by four primary end-points: pain intensity as measured by a 100-mm visual analogue scale hourly for 12 h, time to rescue analgesic, postoperative analgesic consumption, and patient's global assessment. Throughout the 12-h investigation period, patients reported significantly lower pain intensity scores in the ketorolac pretreated sides when compared with the post-treated sides (P = 0.003). Patients also reported a significantly longer time to rescue analgesic (8.9 h versus 6.9 h, P = 0.005), lesser postoperative analgesic consumption (P = 0.007) and better global assessment for the ketorolac pretreated sides (P = 0.01). Pretreatment with intravenous ketorolac has a preemptive effect for postoperative third molar surgery and extended the analgesia by approximately 2 h.     

Influence of ultrasound on the percutaneous absorption of ketorolac tromethamine in vitro across rat skin

The influence of ultrasound on percutaneous absorption of ketorolac tromethamine was studied in vitro across rat skin. Sonication was carried out with a continuous mode, at an intensity of 1-3 W/cm² and a frequency of 1 MHz for 30 min. A significant increase in permeation of ketorolac through rat skin was observed with the applied sonication at 3 W/cm² when compared with permeation at 1 and 2 W/cm². Enhanced ketorolac penetration at 3 W/cm² can be explained by the mechanical and/or thermal action of ultrasound waves. The distance of the ultrasound probe from the skin surface did not influence the flux of the drug. Pretreatment of skin by 5% d-limonene in ethanol for 2 hr followed by sonication at 3 W/cm² (30 min) significantly enhanced the permeation of ketorolac when compared with passive flux with or without enhancer pretreatment.     

In vitro iontophoretic transport of ketorolac: synthetic membrane as a barrier

The effect of different factors on the iontophoretic transport of ketorolac was analyzed. In vitro experiments were performed in a diffusion cell with a cellulose membrane as a barrier. The results indicated that an increase in current density or drug concentration enhanced the transmembrane permeation of the drug. The presence of extraneous ions (such as NaCl) or an increase in viscosity of the donor medium slowed down the iontophoretic transport of the drug. The pH does not seem to be an important factor determining iontophoretic transport of ketorolac as statistically insignificant difference was observed in flux at pH 5.6, 7.2, and 8. Also, the relative importance of the transport contributions involved in iontophoresis, namely diffusive iontophoretic and electro-osmotic fluxes, was investigated using glucose as a nonionizable drug. The results indicated that the total flux of ketorolac is a result of two contributions: passive diffusion and iontophoretic flux. The contribution of electro-osmosis appears to be negligible.     

A randomized, controlled trial to compare ketorolac tromethamine versus placebo after cesarean section to reduce pain and narcotic usage

Objective

The purpose of this study was to determine whether postcesarean section administration of ketorolac tromethamine reduces pain and narcotic usage.

Study design

A double-blinded randomized, placebo-controlled trial of ketorolac tromethamine was performed. Patients were randomly assigned to receive either ketorolac tromethamine or placebo. Patient-controlled analgesia (PCA) was used for pain control. Visual analog scales (VAS) were administered postoperatively to assess pain levels. Morphine equivalents and attempts were recorded.

Results

There were 22 patients in each arm of the study. There was no significant difference between patient demographics, blood loss, and type of anesthesia. Pain scores were significantly different at 2, 3, 4, 6, 12, and 24 hours by analysis of variance (ANOVA) (P = .033). There was a significant decrease in pain medication usage (P = .008) in the study group.

Conclusion

Ketorolac tromethamine is efficacious in reducing postoperative pain and narcotics usage after cesarean section.     

吉法酯与安贺拉眼液联合应用治疗碱灼伤干眼的实验研究

目的探讨吉法酯(Gefarnate)与安贺拉眼液联合应用对碱灼伤干眼兔模型的治疗作用。方法新西兰白兔20只(40眼),制作碱灼伤干眼模型,随机分成对照组和实验组,分别滴生理氯化钠、1%Gefarnate联合0.5%安贺拉滴眼液。行定期裸眼、结膜荧光素染色、虎红染色、泪膜破裂时间(Tear break-up time,BUT)、泪液蕨样变试验(Tear ferningtest,TFT)等检查,第7、28天分别取结膜免疫组织化学检测黏蛋白5AC(MUC5AC)表达和炎性细胞浸润情况。结果实验组裸眼体征缓解,结膜荧光素染色、虎红染色逐渐减轻,与对照组比较有统计学意义(P<0.05);BUT术后逐渐下降,第7天最明显,随后逐渐升高,与对照组比较有统计学意义(P<0.05);TFT显示实验组Ⅲ、Ⅳ级结晶逐渐减少;结膜杯状细胞密度第7天开始增加,MUC5AC阳性率和积分在第28天升高,与对照组比较有统计学意义(P<0.05);实验组第7、28天炎症细胞浸润密度减少,与对照组比较有统计学意义(P<0.05)。结论Gefarnate联合安贺拉滴眼液是治疗碱灼伤所致干眼症的一种好而有效的方法。     

高效液相色谱法测定人尿中酮洛酸含量

目的建立以高效液相色谱法测定人尿中酮洛酸浓度的方法。方法色谱柱为Waters Sunfire C18,流动相为0.02mol·L-1磷酸二氢钾溶液-乙腈(70∶30,用磷酸调节pH值至4.5),检测波长为315nm,柱温为35℃,流速为1mL.min-1,进样量为20μL,保留时间为9.1min。结果人尿中酮洛酸浓度在0.1～10.0μg·mL-1范围内线性关系良好,日内和日间RSD<10%,最低定量限为0.1μg·mL-1。结论本法简便、快捷、灵敏,适用于酮洛酸人体药动学研究。     

Evaluation of skin permeation and accumulation profiles of a highly lipophilic fatty ester

The aim was to evaluate the skin permeation and accumulation profiles of a highly lipophilic fatty ester using the combination of various permeation enhancing techniques to study the potential of highly lipophilic fatty esters as local topical agents. Permeation and accumulation profiles of ketorolac stearate (C18:0) were studied using solubility improved formulation, supersaturated solution of permeant in enhancer vehicle, lipophilic receptor solution, enhancer pretreatment, and the removal of stratum corneum and delipidization of skins. Impermeability and minimal skin accumulation of ketorolac stearate could delineate a preliminary possibility for designing safer topical agents without systemic absorption.     

酮咯酸通过胰岛素样生长因子2信号通路抑制卵巢癌的生长和转移

目的 探讨酮咯酸对卵巢癌生长、转移影响及机制。方法 实验于2019年8月至2020年3月进行。细胞计数试剂盒（CCK-8）法检测不同剂量（0.10 g/L、0.50 g/L、1.00 g/L、1.50 g/L）酮咯酸对人卵巢癌细胞SKOV3的抑制率,筛选酮咯酸的最佳作用浓度。SKOV3细胞分为NC组、酮咯酸组、DMSO组、Linsitinib组、酮咯酸+pcDNA 3.1组和酮咯酸+pcDNA 3.1-IGF2组,TraNCwell法检测各组细胞迁移和侵袭,蛋白质印迹法（Western blotting）法检测各组细胞中胰岛素样生长因子2(IGF2)、胰岛素样生长因子1受体（IGF1R）的蛋白表达。裸鼠分为NC组和酮咯酸组,每组10只,观察酮咯酸对肿瘤生长及肿瘤组织中IGF2、IGF1R的蛋白表达的影响。结果 与NC组相比,不同剂量（0.10、0.50、1.00、1.50 g/L）酮咯酸组细胞抑制率升高[（6.99±0.06）%、（23.31±2.11）%、（51.39±6.91）%、（76.14±4.36）%比（0.02±0.00）%,P <0.05],选择1.0 g/L酮咯酸...