青蒿琥脂和复方奎方治疗恶性疟疾268例疗效分析

目的探讨青蒿琥脂和复方奎方治疗恶性疟疾疗效。方法 268例患者确诊后即采用青蒿琥脂治疗,同时给予对症治疗。入院第2日起检查外周血,如发现疟原虫未转阴则每日继续静注至1个疗程最高剂量480mL;治疗后4d起,患者每天服磷酸伯氨喹啉,连服4d。用青蒿琥脂达1个疗程最高剂量而疟原虫未见转阴,或1个月内复发者,用法国产复方奎方和复方维生素B进行治疗,连续治疗2d。结果青蒿琥脂方案治愈241例,治愈率为90%。死亡8例;复方奎方治愈18例,治愈率为95%,死亡1例。结论青蒿琥脂与磷酸伯氨喹啉配伍治疗,可作为常规治疗恶性疟疾的方法,国内治疗恶性疟疾方法亦有待探讨和改进。     

青蒿琥酯治疗在马里共和国的恶性疟疾321例

目的 :观察青蒿琥酯对恶性疟疾的疗效。方法 :96 1例恶性疟疾病人随机分成青蒿琥酯组 32 1例 (男性 152例 ,女性 16 9例 ) ,用青蒿琥酯 6 0mg +5%葡萄糖注射液 5mL ,iv ,qd ,首剂加倍 ,疗程 5d ;奎宁 雷琐辛组 32 0例 (男性 140例 ,女性 180例 ) ,用奎宁 雷琐辛 50 0mg + 5%葡萄糖注射液 50 0mL ,iv ,gtt ,qd ,疗程 3d ;氯喹组 32 0例 (男性 143例 ,女性 177例 ) ,用氯喹 50 0mg ,po ,qd ,首剂加倍 ,疗程 3d。各组经 1个疗程治疗后未愈者 ,均继续治疗 1个疗程。结果 :治愈率青蒿琥酯组为 10 0 % ,奎宁 雷琐辛组为 97.5% ,氯喹组为 6 7.2 %。青蒿琥酯组第 2疗程和第 1疗程治愈率分别为 10 0 %和82 .6 % (P <0 .0 1) ,复燃率为 2 .8% ,无不良反应。结论 :青蒿琥酯治疗恶性疟疾安全有效     

青蒿琥酯与奎宁治疗疟疾的疗效比较

目的：了解青蒿琥酯对疟疾的疗效。方法回顾性分析2008年至2010年两年期间925例疟疾患者的临床资料,比较青蒿琥酯或奎宁治疗疟疾的疗效。结果青蒿琥酯组治愈率达91.39%,与奎宁组（31.71%）比较差异有显著性;青蒿琥酯组不良反应小,仅在消化系统（4.39%）以及心血管系统（1.88%）存在不良反应,而奎宁组不良反应明显小,两组比较差异有显著性。结论青蒿琥酯与奎宁相比治疗疟疾起效快、治愈率高、复燃率低、副作用小的特点,值得大力推广。     

3种用药方案治疗恶性疟疾的最小成本分析

目的对比分析3种不同用药方案治疗恶性疟疾的最小成本。方法选择性地将无其他并发症的1440例恶性疟疾患者随机分为A组（青蒿琥酯片加阿莫地喹片）、B组（双氢青蒿素哌喹片）、C组（复方磷酸萘酚喹片）,运用药物经济学方法进行回顾性分析。结果 A、B、C 3组有效率分别为98.75%、98.33%、98.54%,成本分别为45.8、48.7、24元。3组病例中,都有个别病例出现比较轻微的恶心、胃不适、谷丙氨基转移酶及谷草氨基转移酶一过性轻度升高等不良反应,停药后可自行恢复正常。结论 3组疗效比较无显著性差异（P〉0.05）,C组治疗方案成本最低,最为经济。     

青蒿琥酯联用伯氨喹治疗迁延、复燃疟疾的临床研究

目的:探讨青蒿琥酯联用伯氨喹治疗迁延、复燃疟疾的临床疗效。方法:将82例患者随机分成治疗组和对照组各41例。治疗组:给予青蒿琥酯和伯氨喹:青蒿琥酯首剂2.4 mg/kg i.v.,12 h后予1.2 mg/kg青蒿琥酯,随后6 d每日以1.2 mg/kg青蒿琥酯同法给予;同时加服伯氨喹片22.5 mg q.d.。对照组:给予quini max,首剂20 mg/kg,i.v.gtt,12 h后予10 mg/kg,随后每日12 h给予10 mg/kg,直至患者能口服,改口服quini max片10 mg/kg,q.8.h,疗程7 d。结果:7 d后治疗组、对照组治愈率分别为97.5%、95.1%;28 d治疗组、对照组治愈率分别为97.5%、90.2%,治疗组与对照组变化相近(P>0.05);两组的退热时间分别为28.0、51.6 h,血中疟原虫清除时间分别为30.4、59.5 h,治疗组较对照组均降低(P<0.01)。结论:青蒿琥酯联用伯氨喹治疗疟疾作用迅速,副作用小,低复燃率,且对耐奎宁株有效,可作为迁延、复发疟疾以及用奎宁等传统抗疟药治疗失败的首选方法。     

对具有多种药物抗药性的疟疾治疗方案评估

据一国际研究小组报道，双氢青蒿素／哌喹（dihydroareemisinin／piperaquine）片（Ⅰ）在治疗多药耐受恶性疟原虫和间日疟原虫方面比青蒿琥酯加阿莫地喹（artesunate＋amqdiaquine）（Ⅱ）更为有效。     

青蒿素生物合成研究成热点

青蒿素是我国科研人员从传统中医药青蒿中提取出来并自主研发的一种抗疟疾特效药。20世纪70年代,我国科技工作者从青蒿中分离提纯出一种抗疟活性单体——青蒿素,以后又确定了它的分子结构和构型。1986年我国自主研发的蒿甲醚油针剂、青蒿琥酯钠盐的水针剂以及青蒿素栓剂等抗疟疾药作为一类新药在我国批准生产。1995年蒿甲醚率先被收入国际药典,这是我国首次得到国际认可的自主研发新药。目前,青蒿素系列抗疟药已有5种新药（青蒿素、青蒿琥酯、蒿甲醚、双氢青蒿素、复方蒿甲醚）共9种剂型上市并在世界各国销售,每年挽救了数百万重症疟疾患者的生命。     

青蒿琥酯治疗脑型疟疾32例

目的：探讨青蒿琥酯治疗脑型疟疾的临床疗效。方法：恶性疟原虫引起的脑型疾患者64例，随机分成治疗组和对照组各32例，治疗组给予青蒿琥酯，首剂2.4 mg·kg 1，将其溶于5%碳酸氢钠溶液1 mL，加5%葡萄糖溶液10 mL稀释，缓慢静脉注射，12 h后以1.2 mg·kg 1同法给予，随后6 d每日以1.2 mg·kg 1同法给予；对照组给予奎宁，首剂20 mg·kg 1，将其溶于5%的葡萄糖注射液500 mL，静脉滴注，4 h内输完，8 h后，以10 mg·kg 1维持剂量同法给予，随后每8 h给予10 mg·kg 1，直至患者能口服，改口服奎宁片10 mg·kg 1，q 8 h，直至完成7 d的疗程。结果：治疗组起效快，能迅速地控制疟疾症状，7 d治愈率治疗组90.6%，对照组87.5%，差异无显著性(P＞0.05)；两组的退热时间分别为24和48 h，血中疟原虫清除时间分别为30和60 h，均差异有极显著性(P＜0.01)。结论：青蒿琥酯治疗恶性脑型疟疾作用迅速，副作用小，对耐奎宁株有效，可作为奎宁治疗失败的首选药物。     

青蒿琥酯片含量测定的方法学研究

目的：对青蒿琥酯片含量测定进行方法学研究。方法：采用高效液相色谱法对青蒿琥酯片进行含量测定。结果：采用该方法测定青蒿琥酯片,以浓度对吸收度进行线性回归,青蒿琥酯在1-6mg/ml范围内浓度与吸收度呈良好的线性关系。日内平均回收率101.1%,RSD为0.77%;日间平均回收率101.6%,RSD为0.80%。结论：本法测定青蒿琥酯片准确、可靠、重复性好,可用于该产品的质量控制。     

抗疟药青蒿琥酯的研究

综述我国创制的抗疟新药青蒿琥酯的药理与临床应用进展,青蒿琥酯给药后在体内血浆中的浓度远大于体外对恶性疟原虫的最小抑制浓度,临床上清除疟原虫９５％所需时间仅为１６小时,临床应用数千例未见明显的毒副作用;可通过口服,静注,肌注及直肠等多种途径给药,青蒿琥酯的半衰期短,可能有利于延迟抗性的产生。该药已成为对恶性疟有快速治疗效果且耐受性好的抗疟药,现已在亚,非,拉等疟疾流行区被广泛用于治疗各种疟疾,是治疗     

Dihydroartemisinin/Piperaquine: a review of its use in the treatment of uncomplicated Plasmodium falciparum malaria

Artemisinin-based combination regimens are recommended by WHO for the treatment of uncomplicated Plasmodium falciparum malaria. One such combination comprises the artemisinin derivative dihydroartemisinin and the bisquinolone piperaquine. Eurartesim? is the only dihydroartemisinin/piperaquine formulation that meets international good manufacturing practice standards. This article reviews the pharmacological properties of dihydroartemisinin and piperaquine, and the therapeutic efficacy and tolerability of dihydroartemisinin/piperaquine in the treatment of uncomplicated P. falciparum malaria. A number of trials have shown dihydroartemisinin/piperaquine to be highly effective in the treatment of uncomplicated P. falciparum malaria. Two pivotal, randomized, open-label, multicentre trials demonstrated the Eurartesim? formulation of dihydroartemisinin/piperaquine to be noninferior to artesunate plus mefloquine in children and adults in Asia and noninferior to artemether/lumefantrine in children in Africa, in terms of polymerase chain reaction-corrected cure rates. In both trials, dihydroartemisinin/piperaquine recipients were significantly less likely than artesunate plus mefloquine recipients or artemether/lumefantrine recipients to experience reinfection. Gametocyte carriage was greater in patients receiving dihydroartemisinin/piperaquine than in those receiving comparator antimalarial regimens. The Eurartesim? formulation of dihydroartemisinin/piperaquine was generally well tolerated in the treatment of uncomplicated P. falciparum malaria, and was associated with significantly less nausea, vomiting and dizziness than artesunate plus mefloquine. Although prolongation of the corrected QT interval has been reported in patients receiving dihydroartemisinin/piperaquine, there are currently no clinical data signalling that it is associated with clinically significant arrhythmias. In conclusion, dihydroartemisinin/piperaquine is a valuable option for use in the first-line treatment of uncomplicated P. falciparum malaria.     

Chemical Stability of Artesunate Injection and Proposal for its Administration by Intravenous Infusion

Artesunate, the only artemisinin analogue that can be given intravenously, produces rapid parasite and fever clearance in falciparum malaria. A significant therapeutic problem is a high, late recrudescence rate, probably due to short half-lives of both artesunate and its active metabolite dihydroartemisinin relative to conventional dosing intervals. One method of extending the duration of action of artesunate could be to administer the drug by infusion rather than bolus injection, provided that it is chemically stable at ambient temperature. Artesunate was found to be stable in 0m?9% w/v sodium chloride at 9°C, 23°C and 36m?5°C for 130, 10m?6 and 1m?6 h, respectively. Interpolating from an Arrhenius plot, artesunate should be stable for approximately 4 h at 30°C, a temperature representative of ambient conditions in tropical countries. Exposure to light did not affect the degradation rate. Single compartment pharmacokinetic modelling was used to evaluate potential differences in artesunate and dihydroartemisinin plasma concentrations following administration of artesunate by intravenous bolus or infusion. A bolus injection of artesunate at a dose of 4 mg kg^?1 gives a peak concentration of 5m?3 mg L^?1, falling to 0m?005 mg L^?1 at 5 h. The same dose infused over 4h results in a peak concentration of 0m?92 mg L^?1 falling to 0m?005 mg L^?1 at 8h. Simultaneous modelling of dihydroartemisinin showed that while its peak plasma concentration was reduced by 27% and the peak delayed by 2.5 h following artesunate administration by infusion, substantially higher concentrations were maintained compared with those predicted after bolus artesunate. These data indicate that artesunate can be administered as a high-dose intravenous infusion, thus avoiding high plasma concentrations. This strategy also has the potential to prolong the duration of antimalarial effect and reduce toxicity, and consequently improve clinical outcome in seriously ill patients.     

Opposite malaria and pregnancy effect on oral bioavailability of artesunate – a population pharmacokinetic evaluation

Aim

The aim was to compare the pharmacokinetic properties of artesunate and dihydroartemisinin in the same women: i) pregnant with acute uncomplicated malaria on day 1 and 2, ii) pregnant with convalescent malaria on day 7 and iii) in a healthy state 3 months post-partum on day 1, 2 and 7.

Methods

Non-linear mixed-effects modelling was used to compare plasma concentration–time profiles of artesunate and dihydroartemisinin over 7 days of treatment following oral and intravenous artesunate administration to pregnant women with uncomplicated Plasmodium falciparum malaria during their second or third trimesters of pregnancy. The same women were restudied 3 months after delivery when fully recovered. Non-compartmental results of the same study have been published previously.

Results

Twenty pregnant patients on the Thailand-Myanmar border were studied and 15 volunteered to be restudied 3 months post-partum. Malaria and pregnancy had no effect on the pharmacokinetic properties of artesunate or dihydroartemisinin after intravenous artesunate administration. However, malaria and pregnancy had opposite effects on the absorption of orally administered artesunate. Malaria increased the absolute oral bioavailability of artesunate by 87%, presumably by inhibiting first pass effect, whereas pregnancy decreased oral bioavailability by 23%.

Conclusions

The population pharmacokinetic analysis demonstrated opposite effects of malaria and pregnancy on the bioavailability of orally administered artesunate. Lower drug exposures during the second and third trimesters of pregnancy may contribute to lower cure rates and thus the development of drug resistance. Dose optimization studies are required for artesunate containing artemisinin-based combination therapies (ACTs) in later pregnancy.     

Pharmacokinetics of oral artesunate in thai patients with uncomplicated falciparum malaria

The pharmacokinetics of artesunate and its major plasma metabolite, dihydroartemisinin, were investigated in 11 Thai male patients with acute uncomplicated falciparum malaria during the acute and recovery phases. Patients were given an oral dose of 200mg artesunate (Guilin Pharmaceutical) on the first day, followed by 100mg 12 hours later, then 100mg daily for another 4 days (total dose of 700mg). All the patients showed a rapid initial response with median (range) parasite and fever clearance times of 30 (18 to 60) and 24 (4 to 94) hours, respectively; no patients showed reappearance of parasites during the 28-day follow-up period. No significant clinical adverse effects were detected in any patient. Acute phase malaria infection significantly influenced the pharmacokinetics of artesunate and its active metabolite, dihydroartemisinin. Maximum plasma drug concentration (C(max)), absorption half-life (t((1/2)a)), area under the plasma concentration-time curve from zero to the last observed time (AUC) and terminal elimination half-life (t((1/2)z)) of artesunate were decreased, while apparent total body clearance (CL/f) was increased during the acute phase, compared with the recovery phase. In addition, a decrease in the C(max) and an increase in the AUC(DHA/ARS ) ratio were found. Optimisation of therapy with oral artesunate should therefore be based on the kinetics of the drug and dihydroartemisinin in malaria patients with acute phase infection.     

硫酸吗啡控释片直肠给药治疗中晚期癌性疼痛临床疗效观察

目的:评价中晚期癌性疼痛患者应用硫酸吗啡控释片直肠给药的治疗效果和安全性。方法:100例患者随机分为试验组(n=50)与对照组(n=50),试验组先直肠给予硫酸吗啡控释片30mg,12h1次,连用14d,再口服30mg,12h1次,连用14d;对照组先口服给予硫酸吗啡控释片30mg,12h1次,连用14d,再直肠给予30mg,12h1次,连用14d。结果:试验组与对照组组间、组内疼痛缓解率、生活质量改善情况、不良反应发生率比较差异无统计学意义(P>0.05),但直肠给药的镇痛起效时间快于口服给药(P<0.05)。结论:硫酸吗啡控释片直肠给药临床效果确切,不良反应少于口服给药,适用于不能口服或口服不良反应较多的患者。     

复方天麻蜜环糖肽片治疗脑震荡后遗症的临床疗效观察

目的:观察复方天麻蜜环糖肽片治疗脑震荡后遗症的临床疗效。方法:将100例脑振荡后遗症患者随机分为2组:治疗组50例口服复方天麻蜜环糖肽片,每次2片,每日3次;对照组50例应用胞磷胆碱钠注射液0.5～0.75g加入0.9%氯化钠注射液250mL中静脉滴注,每日1次。疗程均为30d。结果:治疗组的有效率为92.0%,对照组的有效率为70.0%,2组之间比较具有显著性差异(P<0.01)。结论:复方天麻蜜环糖肽片治疗脑震荡后遗症疗效确切,能较好地改善患者临床症状。     

阿奇霉素联合莫沙必利治疗糖尿病胃轻瘫的疗效及安全性观察

目的：探讨阿奇霉素与莫沙必利联合治疗糖尿病胃轻瘫的疗效及安全性。方法：糖尿病胃轻瘫患者70例随机分为观察组和对照组。两组患者均予药物控制血糖（胰岛素注射或降糖药口服）。观察组患者予阿奇霉素肠溶片0.25 g,po,qd,莫沙必利片5 mg,po,tid联合治疗,对照组患者予单纯莫沙必利片5 mg,po,tid治疗,两组疗程均为4周。观察两组患者治疗后的临床疗效及药物不良反应,比较治疗后随访1年的复发率。结果：治疗4周后,观察组临床总有效率明显高于对照组（94.29% vs.77.14%,P〈0.05）;两组不良反应发生率比较差异无统计学意义（P〉0.05）。随访1年,观察组复发率明显低于对照组（P〈0.05）。结论：阿奇霉素与莫沙必利联合治疗糖尿病胃轻瘫疗效肯定,安全性较好,并能有效降低患者的复发率。     

还原型谷胱甘肽2种给药方案治疗部分肝切除术后急性肝损害的最小成本分析

目的:对还原型谷胱甘肽2种给药方案治疗部分肝切除术后急性肝损害进行药物经济学评价。方法:将125例接受部分肝切除术后的患者随机分为A组与B组。A组62例,给予还原型谷胱甘肽1.2g静脉滴注(每日1次,10d);B组63例,给予还原型谷胱甘肽1.2g静脉滴注(每日1次,3d)及0.4g口服(每日3次,7d)。观察2组疗效并进行最小成本分析。结果:A、B组总有效率分别为80.65%、80.95%(P>0.05);A、B组总成本分别为1276.54、1117.57元,A组治疗成本明显高于B组(P<0.05)。结论:还原型谷胱甘肽注射剂及口服片剂序贯疗法更符合药物经济学原则。     

玄归止痛滴丸治疗气滞血瘀型偏头痛临床疗效

目的：观察玄归止痛滴丸治疗气滞血瘀型偏头痛的临床疗效。方法：将130例气滞血瘀型偏头痛患者随机分为两组,治疗组100例,服用玄归止痛滴丸,6粒,tid;对照组30例,服用元胡止痛片,5片,tid,两组疗程均为1～7d。结果：治疗组有效率87．0％,对照组为60．0％,两组间比较其结果具有统计学差异（P〈0．01）;治疗组的起效时间、药效维持时间及给药次数等方面均优于对照组,用药后未见明显的不良反应。结论：玄归止痛滴丸对气滞血瘀引起的偏头痛有较好的疗效,且用药安全。