国产甲磺酸托烷司琼正常人体耐受体试验

目的：考察国产甲磺酸托烷司琼正常人体耐受性。方法：24名健康志愿者，随机分为7组，分别参加单次静脉注射甲磺酸托烷司琼3，6，12mg组以及分别po3,6,12,24mg.d^-1，连续5d，结论：2种剂在所试剂量范围内部可耐受。对于神经系统，心血管，肝肾功能及实验室指标无明显显影响；℃6mg.d^-1出现口干，便秘或偶有头痛，耳鸣；口服12，24mg.d^-1主要表现为乏力，恶心，焦虑，腹痛，头晕，嗜睡，鼻塞等；单次静脉注射12mg主要不良反应为焦虑，头晕，腹痛；有1例皮疹。结论：根据耐受性试验结果，建议临床采用d1 6mg iv;d2-d6 6mg po的方案。     

甲磺酸托烷司琼注射液联合地塞米松注射液防治顺铂引起恶心、呕吐的疗效观察

目的观察甲磺酸托烷司琼注射液联合地塞米松注射液防治顺铂引起恶心、呕吐的疗效。方法将90例肺癌、头颈部恶性肿瘤患者随机分为三组,每组30例,对照组（A）化疗前给予甲氧氯普胺注射液＋地塞米松注射液静滴并在化疗后予甲氧氯普胺注射液肌注,对照组（B）化疗前甲磺酸托烷司琼注射液静滴,治疗组（C）化疗前给予甲磺酸托烷司琼注射液＋地塞米松注射液静滴。观察治疗期间三组患者恶心、呕吐的发生情况。结果三组恶心、呕吐差异有显著性,B组较A组恶心、呕吐显著降低,C组较A、B组恶心、呕吐显著降低。结论甲磺酸托烷司琼注射液联合地塞米松注射液防治顺铂引起恶心、呕吐疗效可靠,临床应用安全。     

托烷司琼预防术后镇痛所致恶心呕吐疗效分析

目的比较托烷司琼的不同给药方式对术后恶心、呕吐的预防作用。方法 A组术毕静注托烷司琼5mg后连接镇痛泵;B组术毕静注托烷司琼2mg后镇痛泵内加入3mg;C组托烷司琼5mg加入镇痛泵内。结果与C组比较,A组和B组术后2、4和8h恶心的发生率明显降低。结论在静脉注射2mg的基础上于镇痛泵内加入托烷司琼3mg,可有效预防恶心、呕吐的发生,为最佳给药方案。     

耳穴压豆防治化疗所致呕吐的应用时机研究

目的观察不同时机应用耳穴压豆,防治化疗所致呕吐的疗效。方法本研究以进行含顺铂方案化疗的患者为观察对象,采用随机分组对照的方法,试验组一的患者采用耳穴压豆联合甲磺酸托烷司琼注射液,于化疗前30min开始应用耳穴,试验组二的患者采用耳穴压豆联合甲磺酸托烷司琼注射液,于化疗前24h开始应用耳穴,试验组三的患者采用耳穴压豆联合甲磺酸托烷司琼注射液,于化疗前48h开始应用耳穴,对照组的患者单纯采用甲磺酸托烷司琼注射液。结果在恶心呕吐症状发生情况方面,四组患者中,试验组二的症状发生率最低,持续时间最短,但与其他三组相比,差异无统计学意义(P>0.05),在整体趋势上,试验组减轻化疗所致呕吐的疗效优于对照组。在试验组二中减少化疗所导致的呕吐的情况较好。结论耳穴压豆对于减轻化疗引起的恶心、呕吐具有一定的作用,在化疗前24h开始应用耳穴压豆,疗效较优。     

托烷司琼联合地塞米松预防术后自控静脉镇痛相关恶心呕吐

目的:观察托烷司琼联合地塞米松对手术后患者自控静脉镇痛(PCIA)所致恶心呕吐的防治效果。方法:随机、双盲将160例在连续硬膜外麻醉下行下肢手术的患者分为4组:对照(C)组于手术切皮前(T1)和手术结束时(T2)分别静脉注射生理盐水2mL;托烷司琼(T)组于T1、T2时点分别注射生理盐水2mL和托烷司琼4mg;地塞米松(D)组于T1、T2时点分别注射地塞米松10mg和生理盐水2mL;托烷司琼 地塞米松(T D)组于T1、T2时点分别注射地塞米松10mg和托烷司琼4mg。术毕均行患者自控静脉镇痛(PCIA)。观察术后24h内患者镇痛效果、镇静评分和恶心呕吐发生情况。结果:组间镇痛效果、镇静评分无明显差异。C组恶心呕吐发生率为51.3%,明显高于D组(30.0%)和T组(27.5%)(P<0.05);T D组恶心呕吐发生率为13.2%,与C组比较,P<0.01,与D组和T组比较,P<0.05;各处理组恶心程度均小于对照组(P<0.05);T D组呕吐程度低于C组(P<0.05)。结论:托烷司琼与地塞米松单独应用均能有效地减少手术后PCIA相关的恶心呕吐,减轻恶心程度;两药联用进一步降低患者的恶心呕吐发生率和呕吐的程度。     

托烷司琼对丙泊酚静脉注射痛的预防作用

目的:观察托烷司琼对丙泊酚静脉注射引起的疼痛缓解程度。方法:选择120例ASAI~Ⅱ级的择期手术患者,分段随机法分为4组:I组在施行丙泊酚诱导之前60s给予0.9%氯化钠注射液4mL;Ⅱ组在施行丙泊酚诱导之前60s给予利多卡因40mg;Ⅲ组在施行丙泊酚诱导之前60s,给予托烷司琼2mg;Ⅳ组在施行丙泊酚诱导之前60s给予托烷司琼4mg。所有药物均配成4mL液体,观察每组疼痛的发生率和程度。结果:与对照组相比,托烷司琼和利多卡因一样可以明显降低丙泊酚静脉注射疼痛发生率,托烷司琼2mg与利多卡因40mg效果差异无显著性,而托烷司琼4mg减轻静脉注射痛效果最好。结论:在丙泊酚注射之前60s,利多卡因40mg,托烷司琼2mg,托烷司琼4mg的缓慢注射均可降丙泊酚静脉注射痛的发生率,而托烷司琼4mg是最为有效的方法。     

盐酸托烷司琼在多模式镇痛下的最佳剂量研究

目的探讨盐酸托烷司琼在多模式镇痛中应用的最佳剂量。方法选择240例腹部手术并行多模式镇痛患者,随机分为Ⅰ组、Ⅱ组、Ⅲ组三组,分别在镇痛泵中加入托烷司琼2mg、5mg、10mg,比较术后舒适评分及恶心呕吐的发生情况。结果Ⅰ组患者在各个时间段的VAS评分与Ⅱ组、Ⅲ组对应时间段无统计学意义(P>0.05);Ⅰ组中恶心、呕吐的发生例数分别和Ⅱ组、Ⅲ组比较具有显著差异性,具有统计学意义(P<0.05),Ⅱ组、Ⅲ组之间无显著差异性,不具有统计学意义(P>0.05)。结论使用托烷司琼5mg、10mg于腹部手术后的自控镇痛均能很好的达到有效抑制恶心、呕吐的发生的效果,是一种简单、有效的方法,值得在临床推广。     

托烷司琼联合地塞米松对甲状腺术后恶心呕吐的预防作用

目的:探讨托烷司琼联合地塞米松对甲状腺术后恶心呕吐(PONV)的预防效果。方法:将90例择期行甲状腺手术患者随机分为三组,托烷司琼联合地塞米松(D)组、托烷司琼(T)组及生理盐水(S)组。麻醉诱导前D组静脉注射地塞米松10 mg。手术结束前10 min,D、T组分别静脉注射托烷司琼5 mg,S组静脉注射生理盐水5 mL。观察和记录术后0~12 h,12~24 h,24~48 h内各组发生恶心呕吐的患者数。结果:三组患者恶心的发生率比较,差异无统计学意义(P>0.05)。D组和T组恶心伴呕吐的发生率明显低于S组(P<0.05),D组恶心伴呕吐发生率明显低于T组(P<0.05)。结论:托烷司琼联合地塞米松防治甲状腺术后恶心呕吐效果明显优于单用托烷司琼。     

托烷司琼预防妇科腹腔镜术后恶心呕吐疗效分析

目的评估预先应用托烷司琼对择期妇科腹腔镜手术后恶心呕吐的疗效。方法选择80例ASAⅠ～Ⅱ级行妇科腹腔镜手术的患者,随机分为观察组和对照组,全麻诱导后分别静推托烷司琼5mg和生理盐水5ml。观察两组术后24h内的恶心呕吐情况并作比较。结果观察组术后恶心呕吐的总数降低,术后运用止吐挽救药物明显减少。结论预先应用5mg托烷司琼可有效预防妇科腹腔镜手术后恶心呕吐。     

托烷司琼复合氟哌利多、地塞米松对全麻子宫切除术后恶心呕吐的影响

目的观察托烷司琼复合氟哌利多、地塞米松对全身麻醉子宫切除术患者术后恶心呕吐(PONV)的预防作用。方法择期全身麻醉子宫切除术60例,随机双盲分成A、B两组,每组30例,A组术前给与托烷司琼5mg,B组术前给予托烷司琼2mg、氟哌利多1.25mg、地塞米松10mg。术后随访24h,记录患者术后的PONV的发生率和情况。结果与A组相比,B组术后6h内及6～24h的PONV发生率和程度降低(P<0.05)。结论托烷司琼复合氟哌利多、地塞米松对减少PONV的发生比单独应用托烷司琼效果更好。     

Do cytochrome enzymes influence the therapeutic effect of tropisetron in fibromyalgia?

It is well known that the 5-HT3 receptor tropisetron shows a bell-shaped dose-response curve in the treatment of pain associated with fibromyalgia. The best results are achieved with a daily oral dose of 5 mg for 10 days. Dosages of 10 and 15 mg per day have a much weaker effect. If tropisetron is administered by intravenous injection, a regimen of 5 mg per day over 5 days will suffice to reduce pain substantially. An open study of selected cases revealed that 2 mg of tropisetron daily for 5 days also yielded satisfactory pain reduction, whereas this was not observed in a placebo-controlled double-blind study. We therefore investigated which factors might be responsible for the different effects of the drug. Judging from the above-mentioned studies, the effect of a minimum dosage of tropisetron could be assumed to be partly attributable to the different half-life periods. This is supported by the markedly different rates of constipation, a characteristic side effect of the drug, reported by the two studies.     

中国健康男性志愿者单次口服甲磺酸酚妥拉明片耐受性研究

目的：在中国男性健康志愿中评价单次口服Ⅳ＋Ⅴ类新药甲磺酸酚妥拉明片的安全性、耐受性。方法：根据新药临床试验指导原则设计试验方案，按照赫尔辛基宣言和GCP指导原则，选择18－50岁健康成人，用区组随机化设计方法，按随机表将36名受试随机分配至10、20、30、40、50和60mg剂量组，每组6名受试。观察指标为临床症状、生命体征、心电图、血常规、尿常规、肝功能、肾功能、电解质等。结果：单次口服10-60mg甲磺酸酚妥拉明片，志愿体温、脉搏、呼吸频率、卧立位血压、心电图、血常规、肝功能、肾功能、电解质等各项指标测定值均在正常范围内，仅见面部潮红、鼻塞、头晕头痛或脉率增快（20例）等与药物可能有关的一过性轻微不良反应。9例志愿在给药后20-30min后发生阴茎勃起现象，约持续5min左右。结论：36名中国男性健康受试单次口服甲磺酸酚妥拉明片最大剂量至60mg比较安全、耐受性较好。     

添加托吡酯治疗癫痫的临床研究

目的：观察新型抗癫痫药托吡酯（妥泰）添加治疗癫痫的临床疗效和脑电图（EEG）变化。方法：进行开放性自身对照临床试验，对47例经临床和EEG确诊的癫痫患者在原有抗癫痫药物治疗不变的基础上，添加妥泰治疗，初始剂量为50mg.d^-1，2周后为100mg.d^-1，分2次服用，维持剂量200－400mg.d^-1。以治疗前3个月的发作频度和EEG改变为基础，治疗3个6个月后，分别观察发作频度和EEG的变化，并与治疗前进行比较。结果：添加妥泰治疗3和6个月后，发作次数明显减少，尤以治疗6个月后显著（P＜0．01），总有效率（显效＋有效）分别为61．70％和82．98％，差异显著（P＜0．01）；EEG异常率（高度和中度不正常）也由原来的23．4％和25．5％变为治疗3和6个月后的17．0％和19．1％以及0和10．6％，总异常率由原来的70．2％下降至59．6％和29．8％，差异有显著性（P＜0．01）／。结论：妥泰作为一种辅助抗癫痫药物，不仅能明显减少癫痫的发作频度，使EEG异常率显著降低，而且不良反应少，值得临床推广应用。     

文拉法辛与氯米帕明治疗抑郁症伴焦虑症状的疗效比较

目的 :比较文拉法辛与氯米帕明治疗抑郁症伴焦虑症状的疗效及安全性。方法 :文拉法辛组2 6例 ,用文拉法辛 50～ 2 0 0mg·d- 1,po ,bid～tid ;氯米帕明组 2 4例 ,用氯米帕明 50～ 2 0 0mg·d- 1,po ,bid～tid ;2组均以HAMD ,HAMA ,TESS评定观察 6wk。结果 :对抑郁症状的治疗 ,文拉法辛组与氯米帕明组显效率均为 84 % (P >0 .0 5) ;对伴随的焦虑症状的治疗 ,文拉法辛组显效率为 92 % ,氯米帕明组显效率为 63% (P <0 .0 5)。文拉法辛组常见不良反应为恶心 ( 2 7% )、口干 ( 19% )、便秘( 19% )、震颤 ( 12 % )、乏力 ( 8% )、头晕 ( 8% )等。结论 :文拉法辛治疗抑郁症伴焦虑症状的疗效肯定、耐受性良好 ,而且对焦虑症状的治疗效果优于氯米帕明     

进口盐酸托烷司琼胶囊在中国人体的药代动力学

目的　研究进口盐酸托烷司琼胶囊的人体药代动力学。方法　采用HPLC 二极管阵列紫外法测定 18名健康志愿者口服剂量为 10mg的盐酸托烷司琼胶囊后受试者血浆中的盐酸托烷司琼的浓度。并应用 3P97软件对盐酸托烷司琼的血药浓度 -时间数据进行了拟合 ,求算其药代动力学参数。结果　进口盐酸托烷司琼胶囊的药代动力学参数为 :达峰时间 (Tmax)为 (2 5 3± 0 5 2 )h ,峰值浓度 (Cmax)为 (10 16± 2 89) μg·L-1,曲线下面积AUC0～ 2 4h分别为 (113 6 1±4 0 34)h·μg-1·L-1。结论　进口盐酸托烷司琼胶囊在志愿者体内分布及消除都很快 ,10mg单次给药安全     

环磷酰胺治疗狼疮肾炎的疗效及副作用评价

目的 探讨在使用糖皮质激素的基础上静脉应用环磷酰胺(CYC)治疗狼疮肾炎(LN)的疗效及安全性.方法 随机选择狼疮肾炎患者32例,随访24周.CYC每次剂量0.75 g·m-2体表面积(每次0.6～1.0 g),每月静滴一次或CYC每次剂量0.6 g,每2周静滴一次;同时均联合泼尼松1 mg·kg-1·d-1治疗,病情...     

奈替米星治疗下呼吸道感染41例

目的：了解奈替米星治疗下呼吸道感染的临床疗效。方法：41例下呼吸道感染患者为治疗组（奈替米星200mg.d^-1静脉滴注）,与同期同类30例住院患者作对照（青霉素800万u.D^-1加氨苄西林8．0g.d^-1,静脉滴注）,结果：28．9％,总有效率97．6％。结论：奈替米星治疗下呼吸道感染疗效好,不良反应小,疗程短。     

Pharmacokinetics and metabolism of the 5-hydroxytryptamine antagonist tropisetron after single oral doses in humans.

Tropiestron is a potent and selective antagonist of 5-hydroxytryptamine receptors. Tropisetron was developed for the indication of cancer chemotherapy-induced emesis. The pharmacokinetic and metabolic dispositions of tropisetron were studied in 12 healthy male volunteers receiving a single oral dose of 62 or 312 mumol (20 or 100 mg) of [14C]tropisetron. Serial plasma samples and complete urine and feces were collected for 120 hr postdose. Whereas the absorption of oral doses of 62-312 mumol tropisetron was rapid and complete, bioavailability was estimated to be only 66% for the 312 mumol dose and 52% for the 62 mumol dose, apparently because of saturable first-pass metabolism. Maximal concentrations of tropisetron averaged 87 and 608 nM after doses of 62 and 312 mumol, respectively, and the parent drug accounted for 21 and 36% of the radioactivity in AUC0-24 hr pools. Approximately 90% of the drug was metabolized before excretion, and approximately 70% of the dose was recovered in the urine. Following both the 62 and 312 mumol doses, the terminal half-life of tropisetron averaged 6-7 hr and that of total radioactivity was 10-11 hr. Tropisetron and its metabolites in plasma and urine were separated by gradient elution reversed-phase HPLC. Structures of eight metabolites were assigned on the bases of NMR and MS data. Tropisetron was metabolized by oxidative hydroxylation of the indole ring at positions 5, 6, and 7. The hydroxylated derivatives are further conjugated with glucuronic acid and sulfate. N-Oxygenation and oxidative N-demethylation at the tropinyl nitrogen also occur in trace amounts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers

AIMS: To establish the bioavailability of tropisetron (5 mg) administered orally as capsule compared with 2 mg given intravenously. METHODS: Using a randomized crossover design, 18 healthy volunteers received a single oral dose of tropisetron (5 mg) and an intravenous bolus of tropisetron (2 mg) separated by a wash-out period of 1 week. Plasma concentrations of tropisetron were determined by h.p.l.c. and the pharmacokinetic parameters were estimated. RESULTS: The mean pharmacokinetic parameters for 5 mg tropisetron given orally were Cmax 3.46 ng ml(-1), t(max) 2.6 h, t(1/2) 5.7 h and AUC(0,infinity) 32.9 ng ml(-1) h. After intravenous administration initial plasma concentration was 15.1 ng ml(-1), t(1/2) 5.6 h, AUC(0,infinity) 20.7 ng ml(-1) h, V 678 l and CL 1800 ml min(-1). An inverse correlation was demonstrated between CYP2D6 activity, measured by the sparteine metabolic ratio, and the bioavailability (mean 0.60, range 0.27-0.99) of oral tropisetron. CONCLUSIONS: Tropisetron exhibits a wide range of oral bioavailability at therapeutic doses, which is mainly determined by CYP2D6 activity.     

Single-Dose,Placebo-Controlled,Phase I Study of Oral Dolasetron

Study Objectives . To evaluate the safety, tolerability, and pharmacokinetics of single, escalating doses of oral dolasetron mesylate, a new 5-HT₃ receptor antagonist. Design . Double-blind, placebo-controlled, dose-escalating phase I study. Setting . A clinical research center. Patients . One hundred twenty healthy male volunteers. Interventions . Subjects received either placebo or oral dolasetron mesylate 50, 100, 150, 200, 250, 300, or 400 mg. Measurements and Main Results . Compared with placebo, subjects receiving dolasetron mesylate reported a greater frequency of headache, lightheadedness, dizziness, increased appetite, and nausea. There were no clinically significant changes in mean laboratory values from before to after treatment. Adverse events were transient, mild or moderate, and similar to those after single intravenous doses of the drug. No clinically significant electrocardiographic changes occurred, but lengthening of the QRS complex duration and dose-dependent lengthening of PR and QT_c intervals were observed 1–2 hours after dosing. These effects were asymptomatic and were mainly associated with higher doses (≥ 300 mg). Conclusion . Dolasetron mesylate is well tolerated when administered in single oral doses up to 400 mg to healthy volunteers. Clinical trials are under way to evaluate the agent's efficacy in preventing chemotherapy-induced and postoperative nausea and vomiting with doses up to 200 mg.