Posttonsillectomy vomiting. Ondansetron or metoclopramide during paediatric tonsillectomy: are two doses better than one?

This randomized, double blinded, placebo controlled, prospective study compared the antiemetic efficacy of one preoperative dose of metoclopramide 0.25 mg·kg^?1 intravenously or ondansetron 0.15 mg·kg^?1 intravenously with two doses of the same drugs (second dose administered one h postoperatively) in 200 preadolescent children undergoing tonsillectomy with either isoflurane or propofol anaesthesia. The incidence of posttonsillectomy vomiting was significantly reduced (P < 0.005) by two doses of either metoclopramide or ondansetron (18% and 8%, respectively) compared with placebo (50%). No difference in posttonsillectomy vomiting exists between the children who received isoflurane and those who received a propofol infusion. Our results suggest that two doses of metoclopramide 0.25 mg·kg^?1 intravenously, like two doses of ondansetron 0.15 mg·kg^?1, are effective in reducing vomiting after tonsillectomy in children who have received either isoflurane or propofol anaesthesia.     

A singleiv dose of ondansetron 8 mg prior to induction of anaesthesia reduces postoperative nausea and vomiting in gynaecological patients

The effect of a single intravenous dose of ondansetron in preventing postoperative nausea and emesis (retching and vomiting) (PONV) was investigated in a randomized, double-blind, placebo-controlled, multicentre, international study. Women of ASA class I–III, requiring gynaecological laparotomy, vaginal hysterectomy, or major vaginal surgery were selected for study. Two hundred and thirty-five received placebo, 231 received 1 mg ondansetron, 228 received 8 mg ondansetron and 229 received 16 mg ondansetron, as an infusion over five minutes before the induction of anaesthesia. A standardized balanced anaesthetic technique was employed. This consisted of premedication with either diazepam or temazepam, thiopentone induction, maintenance with nitrous oxide in oxygen supplemented with enflurane or isoflurane, intraoperative analgesia with fentanyl, neuromuscular blockade with any choice of agent and reversal with neostigmine and atropine. Postoperative analgesia was achieved with morphine, and prochlorperazine or metoclopramide were given if a rescue antiemetic was required. A greater percentage of patients in the 8 mg and 16 mg ondansetron groups experienced no postoperative emesis (44% and 39% respectively) than in the placebo and 1 mg ondansetron groups (29% and 28% respectively) for the first 24 hr postoperative period (8 mg vs placebo and 1 mg: P ≤ 0.001; 16 mg vs placebo: P < 0.05; 16 mg vs 1 mg: P < 0.05). Similarly, the percentage of patients who did not experience postoperative nausea were 20%, 26%, 31% and 28% for the placebo, 1 mg, 8 mg and 16 mg ondansetron treatment groups, respectively (8 mg and 16 mg vs placebo P < 0.05). Overall, the incidences of adverse events in the ondansetron and placebo groups were similar. It is concluded that intravenous ondansetron, at doses of 8 mg and 16 mg, is both well tolerated and effective in preventing postoperative nausea and emesis, and no greater benefit was observed with the 16 mg dose in comparison with the 8 mg dose.     

Ondansetron prevents postoperative emesis in male outpatients

Study Objectives: To determine (1) the efficacy and safety of ondansetron in the prevention of postoperative nausea and vomiting (PONV) in male outpatients; (2) prognostic factors for PONV in male outpatients; and (3) patients' perceptions of the debilitating effects of PONV in the ambulatory surgery setting.Design: Prospective, randomized, stratified, double-blind study.Setting: Multicenter—24 medical centers.Patients: 468 ASA physical status I and II males at least 12 years of age scheduled for general anesthesia.Interventions: All patients received intravenous ondansetron 4 mg or placebo prior to undergoing general balanced (opioid) anesthesia.Measurements and Main Results: In the postanesthesia care unit (PACU), the number of emetic episodes, vital signs, adverse events, and nausea assessments were recorded by a blinded observer. After discharge, and until the end of the 24-hour study period, patients completed a diary that collected emetic episodes, adverse events, nausea, and pharmacoeconomic data. There were no differences in patient demographics or safety profiles between groups. The number of patients with no emesis and no nausea during the 24-hour study period was significantly greater (p < 0.05) with ondansetron 4 mg compared with placebo. Prognostic factors for an increased likelihood of developing PONV in males included a history of motion sickness or previous PONV, patients undergoing nonorthopedic procedures, and surgeries lasting longer than one hour. Finally, 38 % of patients experiencing PONV perceived PONV to be as, or more debilitating than, the aftereffects of surgery itself.Conclusions: Ondansetron 4 mg was more effective than placebo in preventing PONV in male outpatients. Males at potential risk for developing PONV include: (1) those with a history of motion sickness and/or PONV; (2) patients undergoing nonorthopedic procedures; and (3) procedures lasting longer than one hour. Such patients may benefit from receipt of a prophylactic antiemetic. Postoperative nausea and vomiting has a debilitating effect that can be differentiated by patients from the effects of surgery itself.     

Effect of PEG6000 on the In Vitro and In Vivo Transdermal Permeation of Ondansetron Hydrochloride from EVA1802 Membranes

The objective was to evaluate ethylene vinyl acetate (EVA) copolymer membranes with vinyl acetate content of 18% w/w (EVA1802) for transdermal delivery of ondansetron hydrochloride. The EVA1802 membranes containing selected concentrations (0, 5, 10 and 15% w/w) of PEG6000 were prepared, and subjected to in vitro permeation studies from a nerodilol-based drug reservoir. Flux of ondansetron from EVA1802 membranes without PEG6000 was 64.1 ± 0.6 μg/cm^2·h, and with 10%w/w of PEG6000 (EVA1802-PEG6000-10) it increased to 194.9 ± 4.6 μg/cm^2·h. However, with 15%w/w of PEG6000, EVA1802 membranes produced a burst release of drug which in turn decreased drug flux. The EVA1802-PEG6000-10 membrane was coated with an adhesive emulsion, applied to rat epidermis and subjected to in vitro permeation studies against controls. Flux of ondansetron from transdermal patch across rat epidermis was 111.7 ± 1.3 μg/cm^2·h, which is about 1.3 times the required flux. A TTS was fabricated using adhesive-coated EVA1802-PEG6000-10 membrane and other TTS components, and subjected to in vivo delivery in human volunteers against a control. It was concluded from the comparative pharmacokinetic study that TTS of ondansetron, prepared with EVA1802-PEG6000-10 membrane, provided average steady-state plasma concentration on par with multiple-dosed oral tablets, but with a low percent of peak-to-trough fluctuation.     

甲泼尼龙合用昂丹司琼防治顺铂引起的急性、迟发性恶心呕吐

目的 :观察甲泼尼龙 (methylprednisolone,甲强龙 )合用昂丹司琼 (恩丹西酮 )治疗以顺铂为主联合化疗引起的呕吐的效果和安全性。方法 :采用随机自身交叉对照方法。 47例患者中 2 3例第 1周期先用甲泼尼龙 80mg和昂丹司琼 8mg ,第 2周期单用昂丹司琼 8mg ;2 4例第 1周期单用昂丹司琼 8mg ,第 2周期用甲泼尼龙 80mg和昂丹司琼 8mg。以上药物均于化疗前 2 0分钟静脉给予 ,每天 1次。每一患者两周化疗药及其剂量相同 (其中顺铂80mg/m2 ) ,止吐药使用天数相同 (一般 2～ 3天 )。结果 :甲泼尼龙合用昂丹司琼和单用昂丹司琼治疗急性呕吐的有效率分别为 93 6 %和 70 2 % (P <0 0 1 ) ,治疗迟发性呕吐的有效率分别为 85 1 %和 65 9% (P <0 0 5) ;对由患者按线性分级计分所得的恶心、食欲、精神状态的疗效合用组明显优于单用组 (P <0 0 1 )。两组治疗不良反应发生率相似且合用组程度较轻。结论 :甲泼尼龙能加强昂丹司琼治疗由大剂量顺铂引起的急性和迟发性呕吐的止吐疗效 ,且能使患者恶心、食欲、精神状态得到明显改善 ,副作用较轻 ,是一较理想的止吐方案     

HPLC-MS研究盐酸恩丹西酮缓释胶囊人体药动学及生物等效性

 目的首次建立人血浆中盐酸恩丹西酮浓度的HPLC-MS分析方法,用以测定健康受试者口服盐酸恩丹西酮缓释胶囊后的血药浓度,估算受试制剂和参比制剂的药动学参数,评价两种制剂的生物等效性和相对生物利用度。方法血浆中加入内标米氮平后,乙酸乙酯提取,HPLC-MS分离、分析。色谱系统:ODS柱(4.6mm×150mm,5μm),甲醇-乙腈-醋酸铵溶液(0.01mol·L^-1)(35∶30∶35)为流动相,流速1.0mL·min^-1,柱温35℃。质谱检测方式:SIM。结果盐酸恩丹西酮的线性范围为0.1～80μg·L^-1(r=0.9999),最低检测质量浓度达0.1μg·L^-1,提取回收率≥85%。口服单剂量和多剂量的盐酸恩丹西酮缓释胶囊后的相对生物利用度分别为(94.1±15.8)%和(94.8±14.3)%。结论本法简便,准确,灵敏度高。统计学结果表明,口服单剂量和多剂量的缓释胶囊与普通参比胶囊相比,达峰浓度低,达峰时间延长,稳态的波动度小,缓释特征明显。经方差分析和双单侧t检验表明,缓释胶囊和普通参比胶囊生物等效。     

盐酸恩丹西酮的高效毛细管电泳手性分离及其大鼠体内立体选择性药动学研究

 目的建立血浆中盐酸恩丹西酮(OND)的高效毛细管电泳手性分离分析方法,并运用该法对盐酸恩丹西酮两对映体在大鼠体内的立体选择性药动学进行研究,同时使用计算机辅助分子模型设计及计算的方法确定两对映体的毛细管电泳峰位。方法以羟丙基-β-环糊精(HP-β-CD)为手性选择剂,测定条件为:分离介质4%HP-β-CD的50 mmol·L^-1磷酸-三乙胺缓冲液(HCl调至pH 2.77);分离电压30 kV,柱温20℃,进样电压30 kV,进样时间45 s,检测波长308 nm;大鼠血浆碱化后,乙酸乙酯提取。结果测定条件下OND基本达到基线分离,大鼠血浆样品测定不受内源性物质干扰。大鼠灌胃给药OND后,经血药浓度随时间变化的测定,计算两对映体在体内的药动学参数,得到两对映体之间在大鼠体内存在立体选择性药动学差异。结论本法简便可靠,可适用于OND在大鼠体内立体选择性代谢研究。