酮咯酸预先镇痛联合罗哌卡因局部浸润用于腹腔镜胆囊切除术患者术后镇痛的效果

目的 探讨酮咯酸预先镇痛联合罗哌卡因局部浸润用于腹腔镜胆囊切除术患者术后镇痛的效果.方法 全凭静脉麻醉腹腔镜下胆囊切除术患者90例,随机分为3组（n=30）：生理盐水组（S组）、0.375％罗哌卡因组（L组）和0.375％罗哌卡因加酮咯酸组（T组）,各组均加舒芬太尼.其中T组于麻醉诱导前15 min静脉注射酮咯酸30 mg.观察术后镇痛效果与不良反应.结果 S组和L组苏醒时间显著短于T组（P＜0.05）.拔管后口述疼痛评分与VAS评分S组最高,L组次之,T组最低（P＜0.05）.S组要求辅助镇痛药者较其他两组多（P＜0.05）.结论 腹腔镜胆囊切除术患者,酮咯酸预先镇痛可优化罗哌卡因局部浸润麻醉的术后镇痛效果.     

卡前列素氨丁三醇治疗产后出血高危因素孕妇的疗效观察

目的：探讨了卡前列素氨丁三醇治疗产后出血高危因素孕妇的疗效观察。方法：回顾性分析我院2010年2月～2013年2月收治的80例产后出血高危因素剖宫产产妇的临床资料,随机分为对照组和观察组,观察组产妇在常规治疗的基础上给予宫体注射卡前列素氨丁三醇治疗,对照组产妇在常规治疗的基础上给予米索前列醇、垂体后叶素宫体注射治疗。结果：产后2h、4h出血量比较,观察组均显著低于对照组,差异有显著性意义(P<0.05);观察组产后出血发生率为12.5%,对照组产后出血发生率为31.91%,两组对比统计学有显著性差异(P<0.05);观察组止血时间显著低于对照组,差异有显著性意义(P<0.05);观察组输血患者2例(5%),输血患者10例(25%),观察组显著低于对照组,两组差异有显著性意义(P<0.05);观察组没有患者行子宫切除术,对照组有2例行子宫切除术,统计学均有显著性差异(P<0.05)。观察组不良反应3例,对照组2例。结论：预防性宫体注射卡前列素氨丁三醇在产后出血高危因素孕妇剖宫产术中能明显减少产后出血量,降低产后出血发生率和输血率,缩短止血时间,减少近远期并发症,值得临床推广。     

无痛肠镜检查中使用酮咯酸氨丁三醇的效果评价

目的：评价酮咯酸氨丁三醇联合丙泊酚静脉麻醉用于无痛肠镜检查的麻醉效果及安全性。方法：选择120例自愿实施无痛肠镜检查患者,随机分为两组,A组仅使用丙泊酚,B组先静脉滴注酮咯酸氨丁三醇30 mg,5 min后静脉推注丙泊酚。记录两组患者在不同时间点的平均动脉压（MAP）、心率（HR）、呼吸（RR）及血氧饱和度（SpO2）数值,比较两组患者的丙泊酚用量、手术时间、术中肢动、清醒时间、疼痛评分。结果：所有患者均顺利完成手术,两组术中的MAP、HR均较术前显著降低（P<0.05）,但两组间比较差异无统计学意义（P>0.05）。B组的丙泊酚用量、疼痛评分、麻醉效果显著优于A组（P<0.05）。两组手术时间、清醒时间比较差异无统计学意义（P>0.05）。结论：在无痛肠镜检查中联合应用酮咯酸氨丁三醇-丙泊酚能增强麻醉效果,不增加麻醉风险,术后腹痛减少,患者满意,是一种安全、有效的麻醉方法,值得在临床上推广应用。     

国产酮咯酸氨丁三醇分散片的人体相对生物利用度研究

目的评价酮咯酸氨丁三醇分散片剂的人体相对生物利用度,并与胶囊剂比较其生物等效性。方法 18名男性健康受试者随机、自身对照交叉单剂量口服酮咯酸氨丁三醇分散片和胶囊,采用RP-HPLC法测定血浆中酮咯酸氨丁三醇的浓度。结果单剂量口服含酮咯酸氨丁三醇20 mg的受试和参比制剂,其达峰时间Tmax分别为(0.68±0.30)、(0.80±0.38)h;血药浓度峰值Cmax分别为(3 124.44±382.96)、(3 170.28±289.03)ng/mL;药时曲线下面积AUC(0→24)分别为(13 939.32±2 471.53)、(14 312.29±2 268.26)ng.h/mL。两种制剂的药物动力学参数比较差异无统计学意义(P>0.05),受试制剂的相对生物利用度(F)为97.86%±11.62%。结论两种制剂具有生物等效性。     

酮咯酸氨丁三醇注射液急诊治疗肾绞痛的临床观察

目的探讨肌内注射酮咯酸氨丁三醇注射液急诊治疗肾绞痛的效果。方法将肾绞痛患者108例随机分为两组,观察组56组例,对照组52例,观察组采用酮咯酸氨丁三醇注射液30mg肌内注射;对照组强痛定50mg肌内注射。结果观察组的临床总有效率明显比对照组（P〈0．01）,起效及显效时间快差异有统计学意义（P〈0．01）,不良反应小。结论采用肌内注射酮咯酸氨丁三醇注射液能有效提高止痛效果,起效快,不良反应小,值得临床推广。     

Pharmaceutical and medical aspects of hyaluronic acid–ketorolac combination therapy in osteoarthritis treatment: radiographic imaging and bone mineral density

Abstract

The objective of this study was to formulate novel painless combined hyaluronic acid (HA)–ketorolac (KT) membrane for the management of osteoarthritis with rapid analgesic onset, thus avoiding HA frequent invasive intra-articular injections and KT gastrointestinal complaints associated with all non-steroidal anti-inflammatory drugs. HA was chemically crosslinked with carbodiimide/glutaraldehyde to yield membrane of low water content. Different in vitro aspects (mechanical properties, water content and in vitro release) were studied leading to an optimized soft, flexible K8 HA membrane containing 30?mg KT that achieved the desired balance of excellent elasticity and low water content. Moreover, a successful retardation of KT release rate was achieved (82%) after 48?h with favored initial fast drug release in the first hour (32.7%) to attain rapid analgesic effect. The clinical assessments in arthritic rats revealed apparent improvement in joint space narrowing, highest increase in bone mineral density at the proximal tibia and distal femur joints with the absence of osteophytosis only in animal group treated with combined HA–KT membrane. Application of K8 membrane was able to preserve KT plasma concentration above its minimum effective concentration for 48?h therefore, would able to replace six commercial tablets each of 10?mg KT.     

Pharmacokinetics and analgesic effect of ketorolac floating delivery system

Abstract

Objectives: The efficacy of ketorolac tromethamine (KT) floating alginate beads as a drug delivery system for better control of KT release was investigated. The formulation with the highest drug loading, entrapment efficiency, swelling, buoyancy, and in vitro release would be selected for further in vivo analgesic effect in the mice and pharmacokinetics study in rats compared to the tablet dosage form.

Methods: KT floating alginate beads were prepared by extrusion congealing technique. KT in plasma samples was analyzed using a UPLC MS/MS assay.

Results: The percentage yield, drug loading and encapsulation efficiency were increased proportionally with the hydroxypropylmethyl cellulose (HPMC) polymer amount in the KT floating beads. A reverse relationship was observed between HPMC amount in the beads and the KT in vitro release rate. F3-floating beads were selected, due to its better in vitro results (continued floating for >8?h) than others. A longer analgesic effect was observed for F3 in fed mice as compared to the tablets. After F3 administration to rats, the C_max (2.2?±?0.3?µg/ml) was achieved at ～2?h and the decline in KT concentration was slower. F3 showed a significant increase in the AUC (1.89 fold) in rats as compared to the tablets.

Conclusion: KT was successfully formulated as floating beads with prolonged in vitro release extended to a better in vivo characteristic with higher bioavailability in rats. KT in floating beads shows a superior analgesic effect over tablets, especially in fed mice.     

缩宫素联合卡前列素氨丁三醇预防剖宫产术后出血的效果评价

目的研究与探讨缩宫素联合卡前列素氨丁三醇对预防剖宫产术后出血的疗效以及护理情况。方法选用2012年4月～2013年4月入住本院成功实施剖宫产术的产妇208例,将其随机均分成两组。对照组给予单纯静脉滴注缩宫素及宫肌注射缩宫素;观察组在静脉滴注缩宫素及宫肌注射缩宫素的基础上,对宫体注射卡前列素氨丁三醇。详细记录两组产妇产后2、24 h的出血量、术中出血量、产后出血以及不良反应情况。结果观察组产妇产后2 h出血量为（141.3±43.2）ml,产后24 h出血量为（241.8±58.7）ml,术中出血量为（101.3±29.2）ml,产后出血1例,未出现不良反应病例;对照组产妇产后2 h出血量为（197.3±59.5）ml,产后24 h出血量为（347.8±83.1）ml,术中出血量为（156.3±40.2）ml,产后出血9例,未出现不良反应病例。观察组产妇术中、术后出血量以及产后出血均显著低于对照组,差异有统计学意义（P〈0.05）,不良反应差异无统计学意义（P〉0.05）。结论缩宫素联合卡前列素氨丁三醇能够有效控制剖宫产术中和术后的出血量,有效抑制产后出血情况的发生,并且十分安全。产妇的病情监测以及药物不良反应的观察护理需加强,只有这样才能将药物疗效提高,降低不良反应的发生。     

Ketorolac tromethamine formulations: an overview

Ketorolac tromethamine (KT) is a non-steroidal anti-inflammatory drug that belongs to the class of heteroaryl acetic acid derivatives. It is a non-selective cyclooxygenase (COX) inhibitor, being marketed in the racemate form. Most of its analgesic and COX inhibitory activity is retained in the S-isomer. Ketorolac is administered as its tromethamine salt orally, intramuscularly, intravenously and as a topical ophthalmic solution. The frequent occurrence of gastrointestinal disturbances including gastrointestinal bleeding, perforation and peptic ulceration along with the short mean plasma half-life (t_1/2 ～ 5.5 h) has prompted for the development of various formulation strategies for the appropriate delivery of KT. The article gives an overview of the main concepts used thus far to design various pharmaceutical dosage forms for the therapeutically effective delivery of the drug candidate through various routes. At present, a great deal of emphasis is being placed on the development of sustained release forms for the drug as this would aid in achieving the required therapeutic efficacy and better tolerance with fewer gastrointestinal side effects.