格拉司琼与恩丹西酮预防化疗后恶心、呕吐的成本-效果分析

目的比较格拉司琼与恩丹西酮预防化疗后恶心呕吐的疗效、不良反应及成本-效果.方法以相关疗效指标及药物经济学成本-效果分析法进行评价,观察药物不良反应.结果格拉司琼预防化疗后恶心、呕吐的有效率分别为83.6%和86.8%,每化疗周期人均费用为210.48元,成本-效果比分别为251.77和242.37;恩丹西酮的有效率分别为72.9%和83.7%,每化疗周期人均费用为381.35元,成本-效果比分别为523.11和456.62.两组患者均未发现不良反应.结论格拉司琼能有效地预防化疗后的恶心、呕吐,成本-效果比优于恩丹西酮.     

Tolerability and Pharmacokinetic Properties of Ondansetron Administered Subcutaneously With Recombinant Human Hyaluronidase in Minipigs and Healthy Volunteers

Background

Subcutaneous ondansetron facilitated by recombinant human hyaluronidase PH20 (rHuPH20) is an alternative for treating nausea/vomiting in patients who cannot receive ondansetron by other routes of administration.

Objective

Based on preclinical results in minipigs, a Phase I study was designed to assess the tolerability and pharmacokinetic properties of subcutaneous ondansetron + rHuPH20 compared with intramuscular, intravenous, or oral ondansetron monotherapy in healthy volunteers.

Methods

In a crossover design, 3 minipigs were dosed with subcutaneous ondansetron 0.08 mg/kg + rHuPH20, or as intramuscular or intravenous monotherapy, for the evaluation of plasma ondansetron concentrations and local tolerability. In a randomized, open-label, 4-way crossover study, subjects received a randomized sequence of SC ondansetron 4 mg + rHuPH20, or ondansetron monotherapy IM (4 mg), IV (4 mg), or PO (8 mg), over 4 daily visits. Study participants included healthy volunteers aged 19 to 65 years with adequate venous access in both upper extremities and no history of QT-interval prolongation. Primary tolerability end points (administration-site observations, systemic adverse events [AEs], and subject-assessed pain) were assessed, and pharmacokinetic parameters (AUC, C_max, T_max, t_½) were computed to compare relative rate and extent of systemic exposure. Results were described using summary statistics, and bioequivalence was determined with a linear mixed-effects model.

Results

In the preclinical study, no adverse events or significant local reactions were observed. The C_max (45.8 ng/mL at 0.08 hour) with subcutaneous administration + rHuPH20 was 83% greater and was achieved 68% faster than with intramuscular administration (C_max = 25 ng/mL at 0.25 hour). In the clinical study, a total of 12 subjects (7 women, 5 men; white majority; mean age, 44.8) were randomized. The majority of AEs were at the injection site, mild in severity, and transient. After subcutaneous administration of ondansetron + rHuPH20, geometric mean C_max was 35% higher than with intramuscular ondansetron, 43% lower than with intravenous ondansetron, and 126% higher than with oral ondansetron (corrected for dose). Bioequivalence tests demonstrated that systemic exposure after subcutaneous administration was similar to that after intramuscular or intravenous administration and significantly greater than that after oral administration.

Conclusions

Subcutaneous ondansetron + rHuPH20 was generally well-tolerated. Subcutaneous dosing resulted in an extent of systemic exposure similar to that with intramuscular or intravenous dosing and greater than that with oral administration, and may be an option for clinical administration of ondansetron. ClinicalTrials.gov identifier: NCT01572012.     

Antiemetic effects of dexamethasone and ondansetron combination during cesarean sections under spinal anaesthesia

Background

Nausea and vomiting are frequently seen in patients undergoing cesarean section (CS) under regional anesthesia. We aimed to compare the antiemetic efficacy of ondansetron and dexamethasone combination with that of the use of each agent alone to decrease the incidence of post-delivery intraoperative nausea and vomiting (IONV) during CS under spinal anesthesia.

Objective

To compare the antiemetic efficacy of ondansetron and dexamethasone combination with that of the single use of each agent to decrease the incidence of postdelivery IONV during CS under spinal anesthesia.

Methods

A randomized, prospective, double blind study was performed on 90 patients undergoing planned CS under spinal anesthesia. Patients received 4mg ondansetron in Group O, 8mg dexamethasone in GroupD, 4mg ondansetron+8mg dexamethasone in Group OD intravenously within 1–2 minutes after the umbilical cord was clamped. Frequency of postdelivery IONV episodes was recorded.

Results

A total of 86 eligible patients were included in the study. There were 29 patients in Group O, 29 patients in Group D and 28 patients in Group OD. There were no statistically significant difference between the groups in terms of baseline characteristics and intraoperative managements. Frequency of intraoperative nausea, retching and vomiting experiences were similar between the groups (p>0.05).

Conclusion

Single dose 4mg ondansetron, 8mg dexamethasone, or combined use of 8mg dexamethasone+4mg ondansetron, given intravenously is all effective agents for the control of postdelivery IONV. Combined use of dexamethasone and ondansetron for the same indication does not seem to increase the antiemetic efficacy.     

Ondansetron rapidly dissolving film for the prophylactic treatment of radiation-induced nausea and vomiting—a pilot study

Introduction

The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient.

Methods

Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting–specific daily diary, the Functional Living Index–Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. “Overall control” was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. “Acute phase” was defined as the days during radiation until the first day after radiation; “delayed phase” was defined as days 2–10 after radiation.

Results

The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires.

Conclusions

Ondansetron rdf is effective for the prophylaxis of rinv.     

磺丁基醚-β-环糊精手性流动相添加剂法分离盐酸昂丹司琼对映体

目的：建立反相高效液相色谱手性流动相添加剂法拆分盐酸昂丹司琼对映体。方法：采用Hedera C18（250 mm×4.6 mm,5μm）柱,考察手性添加剂的种类和浓度、水相pH、缓冲盐的种类和浓度、有机相的种类和比例、柱温等对盐酸昂丹司琼对映体拆分效果的影响。结果：当流动相为10 mmol.L-1NaH2PO4溶液（含5 mmol.L-1磺丁基醚-β-环糊精,磷酸调至pH 3.0）-甲醇（75∶25）,检测波长为310 nm,流速为1.0 mL.min-1,柱温为25℃时,盐酸昂丹司琼对映体可达到基线分离。结论：该方法可实现盐酸昂单司琼对映体基线分离,且操作简便,比手性固定相法更经济。     

恩丹西酮针剂加片剂序贯给药防治每日中等剂量顺铂所致呕吐效果观察

目的　观察恩丹西酮针剂加片剂序贯给药对每日中等剂量顺铂所致急性及迟发性呕吐的防治效果。方法　 5 3例接受含顺铂联合化疗的恶性肿瘤患者分化疗前用恩丹西酮加地塞米松针剂 (a组 )及化疗前后单用恩丹西酮针剂 (b组 )两组 ,从第 2天起两组均用恩丹西酮片剂持续 2d。结果　急性和迟发性 (第 2～ 5天 )呕吐总有效率分别为 94 % ,92 %～ 98% ,两种止吐方案疗效相似。不良反应轻微 ,主要是便秘、头晕。结论　恩丹西酮针剂加片剂序贯给药能有效预防每日中等剂量顺铂所致急性和迟发性呕吐 ;恩丹西酮加地塞米松及单用恩丹西酮具有相似的功效 ,但各有其优势     

治疗围抗癌化疗期病人呕吐疗效探讨

目的：筛选对化疗病人更有效的止吐方法。方法：胃复安为对照组，以 恩丹西酮为主综合用药为观察组进行自身前后对照，以止吐效果为主要指标多侧面观察比较。结果：急性期和延迟期消化道反应防治（0－1，下同）有效率分别是：对照组为42％，28％，观察组为94％，92％，结论：安定，地塞米松，恩丹西酮联合用药是较理想的抗癌化疗止吐处方。     

昂丹司琼和托烷司琼致化学疗法病人顽固性呃逆20例

5-羟色胺3(5-HT3)受体拮抗药对化学治疗(化疗)与放射治疗(放疗)等引起的恶心、呕吐有良好的预防和治疗作用。常见的不良反应有头痛、腹部不适、便秘及胃肠功能紊乱等。我院于2002年10月至2004年9月，2a间发现使用5-HT，受体拮抗药昂丹司琼(ondansetron)与托烷司琼(tropisetron)静脉注射2408例，引起顽固性呃逆20例，发生率占0．83％，现报道如下。     

国产恩丹西酮预防化疗呕吐疗效观察

目的:观察国产恩丹西酮预防化疗呕吐的疗效及其不良反应.方法:224例住院肿瘤化疗病人随机分为两组,(1)丹西酮组(n=120):化疗前20min静注恩丹西酮8mg.(2)胃复安组(n=104);化疗前20min静滴胃复安40～60mg.结果:恩丹西酮组止吐完全缓解率(CR)和总有效率(CR+PR)分别为81.7%(98/120)和97.5(117/120);胃复安组仅18.3%(19/104)和47.1%(49/104);两组比较差异非常显著(P＜0.01).恩丹西酮组不良反应亦较胃复安组明显减少(P＜0.01).结论:国产恩丹西酮预防化疗呕吐效果好且不良反应少.     

地塞米松强化欧必亭、恩丹西酮抗术后恶心、呕吐作用的研究

目的研究病人自控镇痛术条件下地塞米松是否具有强化欧必亭、恩丹西酮抗术后恶心、呕吐(PONV)之作用及其对伤口愈合之影响。方法120名择期手术患者随机分为4组:对照组A给予恩丹西酮8mg;对照组B给予欧必亭3 mg;观察组C给予恩丹西酮8mg+地塞米松10mg;观察组D给予欧必亭3mg+地塞米松10mg。记录术后4、8、12、24 h及2、3d时患者恶心、呕吐情况及伤口愈合等级、时间。结果A组与B组恶心、呕吐差异非常显著(P<0.01);C、D组较A、B组恶心、呕吐显著降低(CvsA,P<0.01;DvsB,P<0.05);观察组与对照组术后伤口愈合等级、时间无显著差异(P>0.05)。结论病人自控镇痛术条件下地塞米松10mg具有明显强化欧必亭、恩丹西酮抗恶心、呕吐作用,该剂量地塞米松对伤口愈合时间及等级无影响。