Penetration-Enhancing Effect of Ethanolic Solution of Menthol on Transdermal Permeation of Ondansetron Hydrochloride Across Rat Epidermis

The aim of this investigation was to study the effect of an ethanol-water solvent system and ehtanolic solution of menthol on the permeation of ondansetron hydrochloride across the rat epidermis in order to select a suitable ethanol-water vehicle and optimal concentration of menthol for the development of a transdermal therapeutic system. The solubility of ondansetron hydrochloride in ethanol, water and selected concenetrtaion of ethanol-water vehicles (20:80 v/v, 40:60 v/v and 60:40 v/v) was determined. The effect of these solvent vehicles, containing 1.5% w/v of ondansetron hydrochloride, on the in vitro permeation of the drug was studied across the rat epidermis. The highest permeation was observed from 60% v/v of ethanol-water vehicle that showed highest solubilty. Hence, the hydroxypropyl cellulose (HPC) (2% w/w) gel formulations containing 1.5% w/w of ondansetron hydrochloride and selected concentrations of menthol (0, 2, 4, 8 and 10% w/w) were prepared using 60% v/v of ethanol-water vehicle, and subjected to in vitro permeation of the drug across rat epidermis. The transdermal permeation of ondansetron hydrochloride was enhanced markedly by the addition of menthol to HPC gel drug reservoir formulations. A maximum flux of ondansetron hydrochloride (77.85 ± 2.85 μ g/cm^2.h) was observed with a mean enhancement ratio of 13.06 when menthol was incorporated at a concentration of 8% w/w in HPC gels. However, there was no significant increase in the drug flux with 10% w/w menthol when compared to that obtained with 8% w/w of menthol in HPC gel formulations. The results suggest that 2% w/w HPC gel drug reservoir formulation, prepared with 60% v/v ethanol-water, containing 8% w/w of menthol provides an optimal transdermal permeation of ondansetron hydrochloride.     

Combining ondansetron and naltrexone effectively treats biologically predisposed alcoholics: from hypotheses to preliminary clinical evidence

BACKGROUND: Individuals considered to be early onset alcoholics (EOA) are characterized by an early onset age, a broad range of antisocial behaviors, high familial loading, and presumed biological disease predisposition. Ondansetron, a 5-HT3 antagonist, improves drinking outcomes and increases abstinence rates among EOA. Individuals with high familial loading for developing alcoholism have lower levels of beta-endorphin and demonstrate a more pronounced increase in beta-endorphin levels in response to alcohol administration compared with individuals who do not have alcoholic relatives. The propensity for naltrexone (a mu opioid antagonist) to reduce alcohol's rewarding effects and drinking in humans is greatest in individuals with high familial loading. Predicated on the added knowledge that 5-HT3 receptors may themselves mediate alcohol reward via activation of the endogenous opioid system, we hypothesized that the combination of ondansetron and naltrexone would act synergistically and would be an effective treatment in EOA. METHODS: We conducted an 8-week double-blind placebo controlled clinical trial in which 20 EOA were randomized to receive ondansetron (4 microg/kg twice a day) + naltrexone (25 mg twice a day) or placebo as an adjunct to weekly standardized group Cognitive Behavioral Therapy. RESULTS: At endpoint, subjects who received ondansetron + naltrexone (n = 10), compared with those who received placebo (n = 10), had fewer drinks/day (covariate adjusted mean 0.99 +/- 0.60 vs. 3.68 +/- 0.63; F1, 16 = 9.35,p = 0.008; effect size = 1.42), drinks/drinking day (covariate adjusted mean 3.14 +/- 0.87 vs. 6.76 +/- 0.71; F1, 13 = 10.45, p = 0.007; effect size = 1.71), and a trend toward increased percent days abstinent (covariate adjusted mean 69.76 +/- 8.64 vs. 48.24 +/- 9.12; F1, 16 = 3.58, p = 0.08; effect size = 0.88). CONCLUSIONS: Ondansetron plus naltrexone seems to synergistically improve the drinking outcomes of EOA. Larger scale studies that test these medications, both alone and together, among various alcoholic subtypes are needed to establish and extend these promising findings.     

曲马多联合昂丹司琼预防剖宫产麻醉后寒颤的效果观察

目的：观察曲马多联合昂丹司琼预防蛛网膜下腔麻醉后寒颤的临床效果。方法将120例行剖宫产的产妇随机分为观察组A、观察组B和对照组。麻醉开始前,观察组A缓慢静脉注射曲马多1mg／kg,观察组B缓慢静脉注射曲马多1mg／kg＋昂丹司琼4mg,对照组给予生理盐水4ml。观察麻醉开始至手术结束4h内产妇寒颤、恶心呕吐、眩晕、低血压、呼吸抑制等不良反应情况和新生儿Apgar评分情况。结果观察组A和观察组B产妇寒颤发生率均低于对照组,差异均有统计学意义（P＜0．05）,观察组A恶心呕吐发生率高于观察组B和对照组,差异均有统计学意义（P＜0．05）,观察组B与对照组恶心呕吐发生率差异无统计学意义（P＞0．05）。3组均未发生眩晕、呼吸抑制等,且术中低血压发生率3组间差异无统计学意义（P＞0．05）,3组新生儿Apgar评分组间差异无统计学意义（P＞0．05）。结论曲马多联合昂丹司琼能有效预防蛛网膜下腔麻醉后的寒颤反应,且恶心呕吐的发生率较低。     

昂丹司琼不同时间及不同剂量给药在预防妇科腹腔镜手术PONV的临床效果

目的探讨昂丹司琼不同时间及不同剂量给药预防妇科腹腔镜手术术后恶心呕吐的临床效果。方法选择全麻下行妇科腔镜手术的患者100例为研究对象,分为四组,每组25例。第一组在麻醉诱导前5rain昂丹司琼8mg静脉注射;第二组手术结束时昂丹司琼8mg静脉注射;第三组麻醉诱导前5min昂丹司琼4mg静脉注射;第四组整个麻醉期间未使用任何抗呕吐药物。比较四组术后24h内恶心呕吐的发生率及程度。结果第一组、第二组、第三组无效例数显著低于第四组,差异均有统计学意义（P〈0．05）。结论昂丹司琼能有效降低术后恶心呕吐的发生率,且临床效果与不同时间和不同剂量无明显关系。     

Potential employment of non-silica-based stationary phases in pharmaceutical analysis

The absolute majority of the HPLC applications use silica-based columns for the separation of active substance and its impurities. However, stationary phases based on metal oxides appear as an interesting alternative. The aim of our study was to investigate the potential utilization of metal oxide-based stationary phases in analytical evaluation of ondansetron and its five pharmacopoeial impurities. In our study commercially available ZrO₂-based columns (e.g. Zr-PBD, Zr-PS, Zr-C18) and TiO₂-based column were used. The effect of an organic modifier (type and ratio), a buffer (type, pH and concentration) and the influence of temperature was investigated. The separation of ondansetron and its five pharmacopoeial impurities was successfully accomplished on a Zirchrom^®-PBD column using a mobile phase consisting of acetonitrile-ammonium phosphate (25 mM, pH 7.0) (18:82, v/v). Detection was performed at 216 nm and the analysis was completed within 7.5 min. The paper proves metal oxide-based stationary phases as an alternative to classical silica-based stationary phases in pharmaceutical analysis.     

昂丹司琼与格拉司琼预防心脏手术后恶心呕吐的随机对照研究

目的探讨预防心脏手术后恶心呕吐（PONV）的方法,对比研究昂丹司琼和格拉司琼对心脏PONV的影响。方法选择气管内插管全身麻醉下行心脏手术的患者90例,随机分成三组,每组各30例。以双盲方式按下述方法给药：Ⅰ组麻醉诱导前静脉注射昂丹司琼4mg（溶于0．9％NaCl溶液20ml）;Ⅱ组麻醉诱导前静脉注射格拉司琼3mg（溶于0．9％NaCl溶液20m1）;Ⅲ组麻醉诱导前静脉注射0．9％NaCl溶液20m。术后12、24h观察记录患者的PONV程度并进行比较。结果Ⅰ组术后12hPONV发生率为20．0％（6／30）,术后24h发生率为26．7％（8,30）;Ⅱ组术后12hPONV发生率为20．0％（6／30）,术后24h发生率为23．3％（7,30）;Ⅲ组术后12hPONV发生率为72．4％（21／29）,术后24h发生率为79．3％（23／29）。Ⅰ、Ⅱ组术后12、24hPONV发生率显著低于Ⅲ组（P〈0．01）,Ⅰ组和Ⅱ组比较差异无统计学意义（P〉0．05）。结论昂丹司琼和格拉司琼对预防心脏PONV均有较好效果,均能有效地降低心脏PONV的发生率,利于患者恢复。     

温和灸在预防化疗消化道反应的疗效评价

目的比较恩丹西酮、恩丹西酮＋奥美拉唑、恩丹西酮＋温和灸三种止吐方案预防化疗消化道反应的疗效。方法以顺铂为主化疗的患者90例,随机分成三组,每组30例,分别使用上述止吐方案,观察其预防化疗消化道反应的效果。结果对于呕吐,单用思丹西酮、恩丹西酮＋奥美拉唑、恩丹西酮＋温和灸三个方案的有效率相近,分别为80％、87％、90％;对于恶心,三个方案的有效率分别为63％、80％,90％,差别具有统计学显著意义（X^2=6．3,P〈0．05）;对于食欲不振,三个方案的有效率分别为17％、53％、80％,有显著差异（x^2=24．27,P〈0．005）。结论单独使用恩丹西酮不足以完全预防化疗引起的消化道反应,加用奥美拉唑后效果有所提高,恩丹西酮＋温和灸效果最好,特别是预防化疗恶心和食欲不振明显优于单用恩丹西酮或恩丹西酮＋奥美拉唑。     

胃复安联合苯海拉明与昂丹司琼治疗化疗后不良反应的观察

目的将两种化疗止吐方法的疗效进行比较,寻找一种高效价廉的止吐方法。方法将200例恶性肿瘤化疗后呕吐患者随机分为胃复安联合苯海拉明止吐治疗组(100例)和昂丹司琼止吐治疗组100例,观察止吐效果和不良反应。结果对于轻度恶心呕吐者,胃复安联合苯海拉明止吐效果与昂丹司琼相近,差异无统计学意义(P>0.05),但对于重度恶心呕吐者,昂丹司琼止吐效果优于胃复安联合苯海拉明(P<0.05)。结论胃复安联合苯海拉明与昂丹司琼对于轻度呕吐的止吐效果均良好,但胃复安联合苯海拉明较昂丹司琼明显价廉。对于重度呕吐者,昂丹司琼的止吐效果较好。