青蒿素哌喹片治疗无并发症恶性疟的剂量探索试验

目的探索青蒿素哌喹片治疗无并发症恶性疟的安全有效的适宜剂量。方法收治7～65岁男性和女性病人共100例,按区组随机化方案分成2组,成人总量1400 mg组年龄(22±s12)岁,1750 mg组年龄(21±12)岁。分别于0h和24h给药一次,比较2组的平均原虫转阴和退热时间、28d治愈率及原虫复燃率。结果2组的平均原虫转阴时间分别是(61±19)h和(57±21)h,平均退热时间为(20±15)h和(18±10)h,P>0.05;28 d治愈率是80%和96%,原虫复燃率为20%和4%,总量1750 mg组显著优于1400 mg组(P<0.05)。2组耐受性均良好,未发现明显的不良反应。结论推荐青蒿素哌喹片的临床治疗剂量为总量1750 mg,每日1次,分2d服完为1个疗程。     

蒿甲醚治疗恶性疟疾与磷酸哌喹的比较

本文试用蒿甲醚给30名恶性疟病人肌内注射与30名恶性疟病人口服磷酸哌喹作对照比较。蒿甲醚“五天疗法”总量480mg,磷酸哌喹“两天疗法”总量1500mg。蒿甲醚平均退热时间为21±10h,平均原虫转阴时间为76±14h,显著快于哌喹对照组。24例随访28d的复燃率为4％,和哌喹相近。蒿甲醚副反应轻,可推荐予临床作进一步研究。     

双咯喹治疗42例疟疾的疗效

我们于1984年8-10月对26例恶性疟患者用抗疟新药双咯喹~2,分别采用1.0g和0.8g的三日疗法进行治疗,平均退热时间分别为50±23h和40±19h;平均原虫转阴时间分别为58±14h和64±15h。同时,对16例间日疟患者采用同样的三日疗法,平均退热时间为28±14h和30±13h;平均原虫转阴时间分别为50±90h和54±11h。恶性疟组与间日疟组均有相应病例数以氯喹作对照。结果表明双咯喹组的临床疗效不逊于氯喹组,但双咯喹的副反应似较氯喹为轻。     

蒿甲醚治疗恶性疟疾现症病人83例

恶性疟疾现症病人108例,其中83例(男56例,女27例;年龄25±14yr)用蒿甲醚80mg,im,qd(首剂加倍)5d为一个疗程;儿童用量递减;其中有脑型恶性疟1例,并发黑尿热者3例;临床治愈率100％,退热时间为37±24h,平均疟原虫无性体转阴时间为47±20h,35d内的复燃率达13％。另外20例用青蒿琥酯60mg,iv,qd(首剂加倍)4d为一个疗程,疗效与蒿甲醚相似。     

酮替芬合并磺胺多辛治疗疟疾现症病人

本文报道应用酮替芬与磺胺多辛、复方治疗疟疾现症病人。在试用的3种复方中,对控制症状、杀灭血内无性体等作用,以酮替芬与磺胺多辛每天分别用6 mg和250 mg(均为成人用量),连续服3d或3.5d的2种方案较佳。用3 d方案治疗间日疟6例与恶性疟3例,它们的无性体平均转阴时间分别为102 h与77 h,平均退热时间分别为57 h与56 h;追踪观察30 d。在6例间日疟中有1例复燃,3例恶性疟未发现复燃。用3.5d方案治疗间日疟3例,它们的无性体平均转阴时间为96h,平均退热时间为54h;追踪30 d未见复燃。服药后的副反应有头痛、思睡等,不需治疗即可自行恢复。因此证明上述复方副反应小,且有较明显的抗疟作用;但例数较小,尚待进一步研究确定。     

蒿甲醚注射液联合复方磷酸萘酚喹片治疗恶性疟疾疗效观察

目的观察蒿甲醚联合复方磷酸萘酚喹片治疗恶性疟疾的临床效果。方法将90名患者随机分成3组,每组30例。A组采用蒿甲醚注射液治疗、B组采用复方磷酸萘酚喹片治疗、C组采用A组和B组联合用药的方式。观察其临床疗效。结果蒿甲醚联合复方磷酸萘酚喹片组平均退热时间、外周血疟原虫转阴时间、平均住院时间、复燃率和复燃天数均小于A、B组相应的观察指标(P<0.05),结果具有统计学意义。蒿甲醚联合复方磷酸萘酚喹片组的总有效率也高于其他两组的有效率(P<0.05),结果具有统计学意义。结论蒿甲醚注射液联合复方磷酸萘酚喹片治疗恶性疟临床效果明显,复燃率低,建议临床使用。     

青蒿琥酯和复方双氢青蒿素序贯治疗对南苏丹恶性疟疾的疗效

目的：观察注射用青蒿琥酯和复方双氢青蒿素片序贯治疗对南苏丹恶性疟疾病人的疗效。方法：回顾性分析2011年7月-2013年11月在南苏丹瓦乌中国二级医院住院的55例恶性疟疾病历。结果：肌注或静脉注射青蒿琥酯注射液（首剂120mg,后60mg/d）1~5d[（3.2±0.9）d],最后一次静脉注射或肌注后24、30、48、72h口服复方双氢青蒿素片2片,共8片。55例疟疾病人的总治愈率为100%,其中3d治愈52例（94.5%）,3~7d治愈3例（5.5%）。4例（7.3%）病人发生恶心、呕吐、腹泻或头晕等轻度不良反应。结论：注射用青蒿琥酯和复方双氢青蒿素片序贯治疗,对南苏丹恶性疟疾病人具有非常好的临床疗效,适合多种人群,耐受性好。     

洛美沙星口服与静脉滴注治疗伤寒的比较

目的 :比较洛美沙星口服与静脉滴注治疗伤寒的临床疗效。方法 :伤寒病人 65例 ,男性 38例 ,女性 2 7例 ,年龄 (36.6±s 2 .8)a ,19～ 5 8a。分治疗组 33例 ,在一般补液、退热的同时加用洛美沙星 0 .3g ,po ,bid ;对照组 32例 ,在一般补液、退热的同时加用洛美沙星注射液 0 .2 g ,iv ,gtt ,bid。 2组均以 14d为一个疗程。结果 :2组发热、嗜酸粒细胞计数恢复至正常的时间治疗组为 (6.9± 1.4 )d ,(11.5± 2 .6)d ,对照组为 (5 .6± 1.2 )d ,(10± 3)d差异有非常显著和显著意义 (P <0 .0 1和P <0 .0 5 ) ,脾肿大等恢复至正常的时间分别为 (10 .1±2 .9)d和 (9.4± 2 .4 )d ,差异无显著意义 (P >0 .0 5 ) ;对照组有效率为 88% ,治疗组为 85 % ,与细菌清除率相一致 ,差异均无显著意义 (P >0 .0 5 )。结论 :洛美沙星口服疗法与静脉滴注疗法治疗伤寒疗效相似     

液相色谱-质谱法测定人血浆中复方赖诺普利及其人体药动学研究

目的:研究液相色谱-质谱法测定人血浆中的复方赖诺普利,并分析高蛋白高脂肪食物对其药动学的影响。方法:采用随机双周期交叉设计,12名健康受试者(男女各半)随机分为2组,Ⅰ组空腹服复方赖诺普利片1片(每片含赖诺普利10．0 mg,氢氯噻嗪12．5 mg),Ⅱ组进食后服复方赖诺普利片1片,交叉间隔为1 wk。结果:空腹和进食单剂量口服受试制剂:赖诺普利的tmax分别为(7．3±s 1．2)和(7．5±1．0)h;cmax分别为(42±7)和(33±10)μg·L-1;t1／2分别为(13．7±2．0)和(12．5±2．2)h; MRT分别为(20±3)和(19．9±2．5)h;AUC0～72分别为(545±147)和(493±125)μg·h·L-1。氢氯噻嗪的tmax分别为(2．8±0．7)和(4．6±1．1)h;cmax分别为(82±23)和(77±13)μg·L-1;t1/2分别为(8．6±1．8)和(8．4±1．7)h;MRT分别为(10．4±2．0)和(11．6±1．6)h;AUC0～48分别为(680±281)和(684±83)μg·h·L-1。结论:该方法选择性强、灵敏度高、操作简便,适用于复方赖诺普利制剂的临床药动学研究;进食高脂肪、高蛋白的食物会影响赖诺普利的达峰浓度和氢氯噻嗪的达峰时间。     

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。     

Pharmacokinetics of halofantrine and n-desbutylhalofantrine in patients with falciparum malaria following a multiple dose regimen of halofantrine

Summary Halofantrine is a new blood schizontocidal drug used for the treatment of multidrug-resistant falciparum malaria. The pharmacokinetics of halofantrine (HAL) and its principal metabolite, N-desbutylhalofantrine (BHAL), was investigated in 6 adult male patients of Melanesian origin with uncomplicated falciparum malaria. The patients received 500 mg of halofantrine hydrochloride at times 0, 6 and 12 h (total 1.5 g).All patients responded to treatment with a mean parasite clearance time of 52.7 h and a mean fever clearance time of 33.8 h. The following kinetic parameters (mean values) were determined for HAL and BHAL, respectively: maximum plasma concentration (C_max)=896 and 491 ng·ml^–1; time to reach the Cmax (t_max)=15 and 56 h; elimination half-life (t_1/2)=91 and 79 h and the mean residence time (MRT)=71 and 102 h.Based on the clinical response the plasma concentrations of HAL and BHAL were adequate for the treatment of uncomplicated falciparum malaria in the 6 patients.     

Safety evaluation of fixed combination piperaquine plus dihydroartemisinin (Artekin) in Cambodian children and adults with malaria

AIMS: To assess the haemodynamic, electrocardiographic and glycaemic effects of piperaquine-dihydroartemisinin (Artekin) fixed combination therapy in uncomplicated malaria. METHODS: Sixty-two Cambodians (32 children and 30 adults) with falciparum or vivax malaria were given Artekin given as four age-based oral doses over 32 h. Supine and erect blood pressure, the electrocardiographic QT interval and plasma glucose were measured before treatment and then at regular intervals during a 4-day admission period as part of efficacy and safety monitoring. QT intervals were rate-corrected (QTc) using Bazett's formula. RESULTS: Artekin therapy was well tolerated and all patients responded to treatment. Average parasite and fever clearance times were 19 and 12 h, respectively. The pretreatment mean fall in systolic blood pressure on standing was 8 +/- 6 mmHg and 6-hourly measurements over 72 h showed no significant change (P = 0.48). There was a significant lengthening of the mean QTc to a maximum of 11 ms(0.5) (95% confidence interval 4-18 ms(0.5)) relative to baseline at 24 h (P = 0.003). The maximal QTc prolongation observed in any patient was 53 ms(0.5). There was a mean 0.4 mmol l(-1) reduction in the post-absorptive plasma glucose during the first 48 h but no episodes of hypoglycaemia (plasma glucose < 3.0 mmol l(-1)) were observed at any time. CONCLUSIONS: Artekin is safe and effective combination therapy for uncomplicated malaria in children and adults. Although piperaquine is a long half-life drug related to other quinoline compounds including chloroquine and quinine, no clinically significant cardiovascular or metabolic effects were observed.     

Atovaquone-proguanil (malarone): an effective treatment for uncomplicated Plasmodium falciparum malaria in travelers from Denmark

BACKGROUND: Previous experience with unacceptable adverse effects with mefloquine as treatment for uncomplicated Plasmodium falciparum malaria prompted an evaluation of the effectiveness and side effects of atovaquone-proguanil (Malarone) in a hospital setting. METHODS: Atovaquone-proguanil was given as standard treatment (1,000/400 mgq.d. for 3 days) to 50 adults who had traveled in Africa and returned with uncomplicated Plasmodium falciparum malaria. Half of the treated patients were African and had lived outside Africa for varying periods of time; the other half were Danish-born persons without any previous immunity towards malaria. RESULTS: All patients treated with Malarone were cured without complications. The mean fever clearance times differed among the groups and according to various degrees of prior exposure to malaria and ranged from 1.3 to 2.2 days. Adverse effects during treatment were mild, and were likely to be due to the malaria itself. Fourteen people who had acquired falciparum malaria in spite of taking proguanil-chloroquine prophylaxis were also cured uneventfully without recrudescence. CONCLUSIONS: Malarone appears to be an effective, safe and acceptable oral treatment for uncomplicated malaria.     

Pharmacokinetics of quinine in African patients with acute falciparum malaria.

The pharmacokinetics of quinine were studied in six Nigerian patients during acute uncomplicated falciparum malaria and convalescent periods. An oral dose of 10 mg/kg quinine dihydrochloride administered 8hourly for 7 days gave parasite and fever clearance times of 36.0 ± 16.6 h and 18.0 ± 6.4 h, respectively. From the individual quinine plasma profiles the mean plasma concentration of quinine at the time of parasite clearance was estimated as 4.5 ± 1.1 g/ml. Plasma quinine levels during malaria rose rapidly reaching a peak around the second and third days and declining thereafter as patients improved clinically. In acute malaria plasma quinine levels were more than two-fold higher than in convalescence; the mean AUC(0-12) in malaria was 37.9 ± 14.7 g.h/ml compared to 17.9 ± 8.5g.h/ml in convalescence. The apparent oral clearance (CL/F) and volume of distribution (Vd/F) duri ng the acute phase of the malaria (1.9 ± 0.7 ml/min/kg and 1.8 ± 0.9 l/kg, respectively) were significantly lower than in convalescence (4.5 ± 2.1 ml/min/kg and 4.2 ± 3.2 l/kg). The present data suggest that malaria parasites in African patients are still very sensitive to quinine and that the current dosage of quinine is effective for the treatment of acute falciparum malaria in African patients without augmenting therapy with any other drug such as tetracycline or sulphadoxine-pyrimethamine. It also confirms that malaria significantly alters the pharmacokinetics of quinine in humans.     

A comparison of the pharmacokinetics of mefloquine in healthy Thai volunteers and in Thai patients with falciparum malaria

Summary We have studied the kinetics of a single oral dose of mefloquine (750 mg) in 12 Thai patients with falciparum malaria and have compared the results with those of a previous study in 12 healthy Thai volunteers [6].All the patients responded to treatment with a mean parasite clearance time of 66.6 h and a mean fever clearance time of 54.1 h.There was no significant difference in peak plasma concentration, time to peak, area under the curve or apparent volume of distribution between patients and controls. However, the terminal half-life (t_1/2) and mean residence time (MRT) were shorter in the patients (12.2 vs 16.7 days for t_1/2 and 15.5 vs 21.4 days for MRT).We conclude that there are changes in the disposition of mefloquine related to malaria, although the exact basis of the changes is not clear.     

A comparison of oral artesunate and artemether antimalarial bioactivities in acute falciparum malaria

AIMS: Artesunate and artemether are the two most widely used artemisinin derivatives in the treatment of uncomplicated Plasmodium falciparum malaria, but there is little information on their comparative pharmacokinetics. The aim of this study was to examine the relative oral antimalarial bioavailability and pharmacokinetics of the two derivatives. METHODS: The pharmacokinetic properties of oral artesunate and artemether (4 mg kg(-1)) were compared in a randomized cross-over study of 14 adult patients in western Thailand with acute uncomplicated Plasmodium falciparum malaria. Antimalarial activity was compared using a previously validated, sensitive bioassay. RESULTS: Despite a 29% lower molar dose, oral artesunate administration resulted in significantly larger mean area under the plasma antimalarial activity time curve and median maximum plasma antimalarial activity than after oral artemether (P 相似文献