Percutaneous Absorption of Nicardipine and Ketorolac in Rhesus Monkeys

Vehicle effects on the percutaneous absorption of nicardipine base, nicardipine hydrochloride, ketorolac acid, and ketorolac tromethamine were determined using the rhesus monkey as an in vivo model for human skin penetration. Vehicles investigated included blends of propylene glycol, trimethylene glycol, ethanol, Azone, Tween 20, water, and long-chain fatty acids. Formulations were prepared such that the compound dose, application area, and percentage saturation of the compound in the vehicle were held constant. Variations in absorption of the compounds were therefore attributable to vehicle effects. Each formulation was applied to three monkeys for a period of 24 hr using 10 Hill Top Chambers. Plasma samples were taken at appropriate intervals for 36 to 48 hr. The results indicated that trimethylene glycol and Tween 20 did not enhance absorption of the test compounds despite claims by other investigators. Azone and ethanol provided moderate enhancement of both the rate and the extent of absorption, while long-chain fatty acids in combination with propylene glycol significantly enhanced penetration. In general, higher fluxes were observed with the more lipophilic compounds nicardipine base and ketorolac acid as compared to the hydrochloride and tromethamine salts.     

盐酸戊乙奎醚减少卡前列素氨丁三醇术中不良反应的效果观察

目的 观察盐酸戊乙奎醚对于剖宫产术中卡前列素氨丁三醇引起的不良反应的影响.方法 选择40例存在子宫收缩乏力危险因素的择期剖宫产的产妇,随机均分为盐酸戊乙奎醚组(A组)和生理盐水组(B组).A组术前静脉注射稀释2 ml的盐酸戊乙奎醚0.5 mg;B组术前静脉注射2 ml的生理盐水.监测两组产妇的MAP、HR、SpO2和RR,记录断脐开始至肌注卡前列素氨丁三醇注射液的时间和术中出血量、输液量、尿量,并观察宫体注射卡前列素氨丁三醇注射液后恶心、呕吐、心悸、胸闷憋气和面部潮红等不良反应.结果 B组产妇恶心、胸闷憋气和面部潮红等不良反应的发生率高于A组(P＜0.05).结论 盐酸戊乙奎醚可有效地减少剖宫产术中卡前列素氨丁三醇注射液引起的不良反应.     

Effect of pretreatment with ketorolac on propofol injection pain

BACKGROUND: : Pain on injection is still a major problem with propofol. We performed this study to compare different doses of intravenous (i.v.) ketorolac with and without venous occlusion and its effect on the incidence and the severity of the pain after propofol injection. METHODS: We conducted a prospective, randomized and double-blind study of 180 patients (20-60 years of age.) scheduled to undergo elective surgery. Six groups of patients were generated: group A received normal saline (NS) 2 ml i.v.; groups B, C, D received ketorolac 10 mg in 2 ml NS with venous occlusion (VO) and a subsequent propofol injection at either 30, 60 or 120 s; groups E and F received ketorolac 15 mg and 30 mg in 2 ml NS and propofol was injected after 60 s. The pain perception was assessed during injection of propofol in all patients. RESULT: : The incidence of propofol-associated injection pain was for A: 46.7%; B: 43.4%; C: 23.3%; D:16.7%; E: 20%, and F: 10%. The incidence of pain following propofol injection was reduced by i.v. ketorolac 10 mg with venous occlusion for 120 s. Furthermore, i.v. ketorolac 15 mg and 30 mg but not 10 mg following propofol injection after 60 s without venous occlusion revealed significant pain reduction when compared to saline group. There was no difference in venous sequelae at 7 days postoperatively between the groups. CONCLUSION: Our results suggested that pretreatment with i.v. 15 and 30 mg ketorolac reduces pain following propofol injection. Moreover, pretreatment with i.v. ketorolac 10 mg with venous occlusion for 120 s achieves the same pain relief effect.     

卡前列素氨丁三醇预防前置胎盘剖宫产产后出血临床研究

目的观察卡前列素氨丁三醇（欣母沛）预防前置胎盘剖宫产产后出血的临床疗效。方法该院从2006年1月～2007年10月因前置胎盘剖宫产62例,其中1例被排除,31例对照组子宫体部注射缩宫素20u及口服米索前列醇400μg,30例治疗组子宫体注射卡前列素氨丁三醇（欣母沛）250μg,两组均予以静脉滴注20u缩宫素。结果治疗组比对照组第3产程时间缩短,产后2h及产后24h平均出血量减少,治疗组产后出血发生率明显少于对照组。结论卡前列素氨丁三醇（欣母沛）预防治疗前置胎盘引起的宫缩乏力性产后出血效果显著。     

酮咯酸氨丁三醇滴眼地兔眼部炎症作用的研究

目的：研究酮咯酸氨丁三醇滴眼液（KTOS）对家兔化学性及外伤性眼部炎症的作用。方法：用巴豆油致炎液经角膜注入眼前房法制备兔眼部急性化学炎症模型;用重物击打眼睑法制备兔眼部急性外伤性炎症模型。将致炎后的动物随机分组给药,并参照眼部炎症评判标准进行评分统计。结果：各KTOS剂量组对外伤性和化学性眼部炎症作用的评分均低于生理盐水组;小剂量KTOS虽有作用,但无统计学意义（P＞0．05）,而中、大剂量KTOS均有明显改善外伤性和化学性眼部炎症的作用（P＜0．05,P＜0．01）;其中对化学性眼部炎症的作用与地塞米松作用相似,对外伤性眼部炎症的作用优于地塞米松。结论：KTOS对外伤性和化学性眼部炎症均有明显的抗炎作用,对外伤性眼部炎症的抗炎作用更强。     

羟考酮降低剖宫产术中卡前列素氨丁三醇所致不良反应的效果

目的观察羟考酮降低剖宫产术中卡前列素氨丁三醇不良反应的效果。方法选取2018年3月至2019年3月廊坊市第四人民医院产科诊治的80例宫缩乏力剖宫产产妇为研究对象,将其随机分为观察组和对照组,每组40例产妇。两组产妇均于胎儿娩出后立即行卡前列素氨丁三醇250μg宫体注射。观察组产妇镇痛泵输入0.5mg·kg-1羟考酮,对照组产妇于胎儿娩出后静脉注射生理盐水2 mL。观察两组产妇卡前列素氨丁三醇注射后2 min(T1)、5 min(T2)、10 min(T3)平均动脉压(MAP)、心率(HR)、血氧饱和度(SpO2)。记录两组产妇术后6h、12h、24h时的视觉模拟疼痛评分(visual analogue scale,VAS)静息痛评分和Ramsay镇静评分,以及两组产妇不良反应发生情况。结果①两组产妇T1、T3时MAP、HR、SpO2比较,其差异均无统计学意义(均P>0.05),观察组产妇T2时MAP、HR明显低于对照组产妇,其差异均具有统计学意义(均P<0.05)。②观察组产妇6h、12h、24 h时的VAS评分明显低于对照组产妇,其差异均具有统计学意义(均P<0.05);12h时的Ramsay评分明显高于对照组产妇,其差异具有统计学意义(P<0.05)。③观察组产妇恶心、呕吐、面部潮红、胸闷憋气、血压升高、头痛眩晕的发生率明显低于对照组产妇,其差异均具有统计学意义(均P<0.05)。结论羟考酮对剖宫产术中卡前列素氨丁三醇所致的不良反应有一定防治作用,有利于产妇生命体征的稳定,具有确切的镇痛和镇静效果。     

卡前列素氨丁三醇联合宫腔纱条填塞治疗宫缩乏力性产后出血效果观察

【摘要】 目的 探析剖宫产后再次妊娠剖宫产子宫收缩乏力应用卡前列素氨丁三醇联合宫腔纱条填塞治疗产后出血的临床效果。方法 选择2015年1月~2017年1月期间收治的剖宫产后再次妊娠剖宫产术中子宫收缩乏力患者70例为研究对象,随机分为两组,其中给予对照组常规止血治疗,而观察组则应用卡前列素氨丁三醇和宫腔纱条填塞联合治疗,对两组的治疗效果进行对比分析。结果 与对照组比较,观察组产后2h和24h出血量均较少,组间比较差异显著（P＜005）;观察组的术后并发症发生率较低,但是组间比较无明显差异（P＞005）;同时,两组的住院时间、血红蛋白含量比较差异有统计学意义（P＜005）。结论 卡前列素氨丁三醇联合宫腔纱条填塞治疗剖宫产后再次妊娠剖宫产子宫收缩乏力性产后出血,具有起效快、效果确切及不良反应少等优点,可安全地用于临床。     

Efficacy of Multimodal Perioperative Analgesia Protocol With Periarticular Medication Injection in Total Knee Arthroplasty : A Randomized,Double-Blinded Study

Pain control is necessary for successful rehabilitation and outcome after total knee arthroplasty. Our goal was to compare the clinical efficacy of periarticular injections consisting of a long-acting local anesthetic (ropivacaine) and epinephrine with and without combinations of an α2-adrenergic agonist (clonidine) and/or a nonsteroidal anti-inflammatory agent (ketorolac). In a double-blinded controlled study, we randomized 160 patients undergoing total knee arthroplasty to receive 1 of 4 intraoperative periarticular injections: Group A, ropivacaine, epinephrine, ketorolac, and clonidine; Group B, ropivacaine, epinephrine, and ketorolac; Group C, ropivacaine, epinephrine, and clonidine; Group D (control), ropivacaine and epinephrine. Compared with Group D, Group A and B patients had significantly lower postoperative visual analog pain scores and nurse pain assessment and Group C patients had a significantly greater reduction in physical therapist pain assessment. We found no differences in other parameters analyzed.     

卡前列素氨丁三醇注射液和缩宫素在剖宫产产后出血中的应用

目的观察卡前列素氨丁三醇注射液（欣母沛）和缩宫素在预防和减少剖宫产产后出血的疗效及其不良反应比较。方法选择2013年11月至2014年3月同济大学附属第一妇婴保健院足月妊娠并行子宫下段剖宫产术的40例产妇为研究对象,并按胎儿娩出后宫体注射药物的不同,将剖宫产术中使用卡前列素氨丁三醇注射液的20例产妇纳入Ⅰ组,将术中使用缩宫素的20例产妇纳入Ⅱ组。观察两组产妇的手术情况和生命体征变化情况。两组产妇年龄、孕龄、体质量等一般情况比较,差异无统计学意义（P〉0.05）。本研究遵循的程序符合同济大学附属第一妇婴保健院人体试验委员会所制定的伦理学标准,得到该委员会批准,分组征得受试对象本人的知情同意,并与之签署临床研究知情同意书。结果Ⅰ组产妇术中出血量显著少于Ⅱ组,两组比较,差异有统计学意义（P〈0.05）。两组产妇用药10min后生命体征变化情况比较,差异有统计学意义（P〈0.05）。Ⅰ组产妇恶心、呕吐、胸闷和颜面潮红等药物不良反应发生率显著高于Ⅱ组,两组比较,差异也有统计学意义（P〈0.01）。结论卡前列素氨丁三醇注射液用于剖宫产术能有效的减少产后出血,但该药物使用时应预防和避免其药物不良反应的发生。     

IN VIVO/IN VITRO CORRELATIONS FOR FOUR DIFFERENTLY DISSOLVING KETOROLAC TABLETS

This study assesses whether in vitro immediate release ketorolac tablet dissolution profiles (utilizing the recently proposed USP dissolution test for ketorolac tablets) can be correlated with in vivo plasma pharmacokinetic parameters. Four batches of ketorolac tablets were utilized: a ketorolac tablet batch that demonstrated a rapid dissolution rate during USP in vitro dissolution testing, two tablet batches that were manufactured such that they dissolved at moderate rates, and a tablet batch that was manufactured such that it dissolved at a distinctly slow rate. The single-dose mean pharmacokinetic characteristics and relative bioavailability of the four different 10 mg ketorolac tromethamine tablets were evaluated in 12 healthy volunteers in a randomized study of Latin square design. The amount dissolved of the various tablets at 10, 20, and 30 min was in the order of fast-dissolving tablets > medium-1-dissolving tablets=medium-2-dissolving tablets > slow-dissolving tablets. In general, the profiles of the average plasma concentrations for ketorolac were similar for the fast- and the two medium-dissolving tablet batches (even though a statistically significant difference was found between the t_max of the fast-dissolving tablet and one of the medium-dissolving tablet batches). The mean plasma concentrations for the slow-dissolving tablet, however, reached peak levels much later, with the peak also being significantly smaller. There were no statistically significant differences in the total AUC or in the mean plasma half-lives among the four formulations. Good correlations were obtained for mean t_max versus the percentage dissolved at 20, 30, and 45 min. Correlations were generally weaker for percentage dissolved versus C_max or percentage bioavailability. This indicates that in vitro dissolution testing for immediate release ketorolac tablets can be a useful indicator of in vivo time to maximum plasma concentration when comparing similarly formulated tablets. Further, the proposed USP dissolution test and specification would have appropriately failed the slow-dissolving tablet batch, which demonstrated a significantly slower rate of absorption as per t_max and C_max.