青蒿素及其两个活性衍生物在狗体内药代动力学的研究

给狗静脉注射青蒿酯6 mg/kg后,血药时程符合一房室模型,药代动力学参数T_1/2为0.45 h,Cl_T为0.2 L/kg·h,Vd为0.15 L/kg。肌内注射蒿甲醚油剂10 mg/kg或30 mg/kg,吸收较快,血药浓度达峰时间分别在给药后4.0或1.9 h,峰浓度分别为0.7和3.7μg/ml。峰后末相消除半衰期分别为4.0和6.5 h。按矩量法计算得MRT值分别为7.0和9.2 h。青蒿素肌内注射后2 h血药浓度达高峰,峰浓度为0.2μg/ml,末相消除半衰期为1.6 h,MRT值为3.3 h。口服或直肠给药。血中未测到青蒿素。     

青蒿琥酯经皮肤吸收治疗猴疟的疗效

青蒿琥酯为高效、速效、低毒的抗疟新药,但近期复燃率较高。为了提高疗效,方便使用,乃研究其经皮肤吸收制剂。青蒿琥酯经皮肤吸收对鼠疟的疗效,在小鼠及兔体内的药代动力学研究已取得较好的结果,现报告对猴疟的疗效。     

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     

青蒿琥酯抗肿瘤作用的实验研究

目的：探讨青蒿琥酯的抗肿瘤作用。方法：采用体内试验以荷瘤小鼠实体瘤重、抑瘤率为实验指标评价青蒿琥酯对S180移植性肉瘤的抑制作用；以荷瘤小鼠存活时间为实验指标评价青蒿琥酯对H22移植性腹水癌的抑制作用。结果：青蒿琥酯能明显抑制实体瘤重，并延长荷瘤小鼠存活时间。结论：青蒿琥酯对S180、H22诱发的移植性肿瘤具有一定的抑制作用。     

高效液相-柱后衍生化法测定青蒿琥酯含量

目的建立测定青蒿琥酯的含量测定方法。方法采用反相高效液相色谱-柱后衍生化法,流动相为乙腈-醋酸盐缓冲液(pH4.0)(60∶40),流速0.8ml/min;衍生试剂为1mol/L氢氧化钾的90%乙醇溶液,流速0.5ml/min;反应温度70℃,柱温30℃,检测波长289nm。结果青蒿琥酯在2～100μg/ml范围内线性关系良好,以峰面积对青蒿琥酯浓度进行线性回归,方程为A=1746.8+8525.4C,r=0.99999;日内、日间精密度RSD均<2%;平均回收率均在98.0%～102.0%。结论该法准确、简便、重现性好,可用于青蒿琥酯的质量控制。     

青蒿琥酯增加小鼠腹腔巨噬细胞内化内毒素、大肠埃希菌的作用及可能机制

目的:观察青蒿琥酯(artesunate,AS)对小鼠腹腔巨噬细胞内化清除脂多糖/内毒素(li-popolysaccharide/endotoxin,LPS)和吞噬大肠埃希菌的影响,并初步探讨其可能的作用机制。方法:MTT法检测不同浓度网格蛋白抑制剂(monodansylcadaverine,MDC)、内体酸化抑制剂氯喹(chloroquine,CQ)对小鼠腹腔巨噬细胞活力的影响,以选择恰当的药物工作浓度;激光共聚焦法检测青蒿琥酯及MDC、CQ对小鼠腹腔巨噬细胞内化FITC-LPS的影响;分别采用激光共聚焦和菌落集落形成计数实验观察青蒿琥酯对小鼠腹腔巨噬细胞内化大肠埃希菌的影响;逆转录PCR检测青蒿琥酯对小鼠腹腔巨噬细胞清道夫受体A(class A scavenger receptor,SR-A)mR-NA表达的影响。结果:MDC和CQ浓度分别小于25μg/mL和20μg/mL时对小鼠腹腔巨噬细胞活力无影响;MDC、CQ可抑制小鼠腹腔巨噬细胞内化LPS,青蒿琥酯可增加小鼠腹腔巨噬细胞对LPS的内化,而且青蒿琥酯可增加MDC和CQ处理的巨噬细胞内化LPS的功能。激光共聚焦和菌落集落形成计数实验均显示青蒿琥酯可增加小鼠腹腔巨噬细胞对大肠埃希菌的内化能力。逆转录PCR结果显示青蒿琥酯可增强LPS处理或未处理的小鼠腹腔巨噬细胞SR-A mRNA的表达。结论:青蒿琥酯可增强小鼠腹腔巨噬细胞内化LPS、大肠埃希菌的能力,该作用可能与SR-A mRNA表达升高有关。     

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。     

青蒿琥酯细菌内毒素检查法研究

目的：建立青蒿琥酯的细菌内毒素检查方法。方法：采用凝胶法,参照《中国药典》2010年版附录ⅪE对青蒿琥酯进行细菌内毒素的方法学研究。结果：样品溶液稀释为0.4mg/ml、0.2mg/ml、0.1mg/ml、0.05mg/ml、0.025mg/ml,通过试验最终判定青蒿琥酯稀释为0.4mg/ml时对细菌内毒素无干扰作用,用灵敏度为0.25EU/ml的鲎试剂进行试验,供试品不干扰细菌内毒素检查。结论：建立的青蒿琥酯的细菌内毒素检查法可行。     

青蒿琥酯对雨蛙素联合脂多糖致急性胰腺炎模型小鼠的治疗作用

目的：明确青蒿琥酯对急性胰腺炎模型小鼠的治疗作用。方法：昆明种小鼠60只,雌雄各半,随机分为正常组、模型组和治疗组,治疗组又分为三个浓度治疗组,即共5组,每组12只。造模方法为：使用雨蛙素（100 μg/kg）连续6次腹腔注射小鼠,每次间隔1 h;最后一次注射雨蛙素后,腹腔注射LPS（10 mg/kg）。治疗组在造模后0 h和4 h肌肉注射不同浓度的青蒿琥酯,于第一次给药后18 h,眼眶取血,测定血清淀粉酶;脱臼处死小鼠,取胰腺组织,进行胰腺组织学观察及组织病理学评分;测定组织脂肪酶、胰蛋白酶以及超氧化物歧化酶的含量。结果：与模型组相比,青蒿琥酯治疗组的胰腺组织病变情况明显减弱,胰腺系数、血清淀粉酶、组织脂肪酶和胰蛋白酶的活力都明显降低（P〈0.05或P〈0.01）,组织超氧化物歧化酶的活力明显升高（P〈0.05或P〈0.01）。结论：青蒿琥酯对急性胰腺炎模型小鼠具有明显的治疗作用,值得继续深入研究。     

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。     

口服双氢青蒿素在兔和狗体内的药代动力学研究

青蒿素是一带有双氧桥结构的倍半萜内酯类抗疟药,已获我国卫生部新药审批委员会批准正式生产,用于临床。青蒿素用硼氢化钠还原得双氢青蒿素,其抗疟作用为青蒿素的4～8倍。我们曾报告给狗po青蒿素50mg/kg后,用放射免疫法在血中未测到青蒿素。     

2,4-二氨基-5-甲基-6-取代苄氨基喹唑啉衍生物的合成及其抗疟和抗肿瘤作用

本文报道2,4-二氨基-5-甲基-6-取代苄氨基喹唑啉衍生物的合成及其抗疟和抗肿瘤活性。这类化合物由5-甲基-2,4,6-三氨基喹唑啉与相应的取代苯甲醛缩合成Schiff碱,然后经还原,甲酰化或亚硝化制得。经对伯氏鼠疟原虫(Plasmodium berghei)抑制性治疗筛选,有三个化合物Ⅳ_(2,5,6)剂量5mg/kg×4d抑制率为100%;体外抗肿瘤活性以Ⅱ_7和Ⅳ_8最强,对L1210白血病细胞株的IC_(50)分别为3.910×10~(-3)μg/ml和6.172×10~(-3)μg/ml,与MTX相当。     

双氢青蒿素在人的药代动力学及与青蒿素的比较

用放射免疫测定法研究青蒿素和双氢青蒿素在人的药代动力学结果:人口服青蒿素片剂15 mg/kg后1.5 h,血药峰值达0.09μg/ml,MRT为3.27 h,而口服双氢青蒿素仅1.1 mg/kg和2.2mg/kg后1.33 h,血药峰浓度分别为0.13μg/ml和0.71μg/ml,MRT分别为2.36和2.26 h,可见,青蒿素片剂的生物利用度仅为双氢青蒿素的1.62%～10.08%,所以口服宜用双氢青蒿素。直肠给青蒿素栓剂15 mg/kg和双氢青蒿素栓剂8 mg/kg后,血药分别于4.6 h和4.7 h达峰浓度0.04 μg/ml和0.11 μg/ml,MRT分别为6.98 h和6.96 h,可见青蒿素栓剂的生物利用度仅为双氢青蒿素者的29%,作为栓剂也可用双氢青蒿素。     

青蒿琥酯在奶牛体内的药代动力学与代谢

青蒿琥酯(artesunate,AS)是抗疟新药青蒿素的一个活性衍生物。近年来我国兽医工作者将其用于治疗牛羊泰勒氏焦虫病及双芽、巴贝斯焦虫病、鸡球虫病和耕牛血吸虫病,也收到了满意的效果。AS在大白鼠、兔、狗及人体内的药代动力学研究已见报道。本     

Ameliorative Effects of Curcumin on Artesunate-Induced Subchronic Toxicity in Testis of Swiss Albino Male Mice

India is one of the endemic areas where control of malaria has become a formidable task. Artesunate is the current antimalarial drug used to treat malaria, especially chloroquine resistant. The objective of the present study was to investigate the dose-dependent effect of oral administration of artesunate on the oxidative parameters in testes of adult male Swiss albino mice and ameliorative efficacy of curcumin, a widely used antioxidant. An oral dose of 150 mg/kg body weight (bwt; low dose) and 300 mg/kg bwt (high dose) of artesunate was administered for a period of 45 days to male mice, and ameliorative efficacy of curcumin was also assessed. The results revealed that artesunate caused significant alteration in oxidative parameters in dose-dependent manner. Administration of artesunate brought about significant decrease in activities of superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase, whereas lipid peroxidation and glutathione-S-transferase activity were found to be significantly increased. The results obtained show that oxidative insult is incurred upon the intracellular antioxidant system of testis tissue by artesunate treatment. Further, administration of curcumin at the dose level of 80 mg/kg bwt along with both doses of artesunate attenuated adverse effects in male mice.     

胍丁胺对伯氏疟原虫K173株的抗疟作用(英文)

AIM: To study the antimalarial effect of agmatine (Agm) on chloroquine-susceptible Plasmodium berghei K173strain (S strain) and the P berghei K173 resistant strain (R strain). METHODS: The antimalarial effects of Agm onP berghei K173 S strain and R strain were evaluated by Peters 4-d suppression test in mice. RESULTS: Agm(12.5-200 mg/kg,ig,daily) decreased the parasitemia for both P berghei K173 S strain (IC50=139 mg/kg) and Rstrain (IC50=126mg/kg) in mice. Subcutaneous injection (sc) of Agm (5-40mg/kg,tid) showed relatively strongerantimalarial effect than intragastric gavage (IC50=30 mg/kg) in P berghei K 173 S strain. Spermidine antagonized theantimalarial effect of Agm for P berghei K173 S strain and R strain. Agm did not reverse the chloroquine resistanceof P berghei K173 S strain, dl-α-Difluoromethylornithine (DFMO, sc) decreased the parasitemia of P BergheiK173 S strain and this effect was antagonized by spermidine. CONCLUSION: Agm has an antimalarial effect andthe mechanism is related to its inhibition of polyamine synthesis.     

阿斯匹林与烟酸联合应用时血药浓度测定

阿斯匹林与烟酸给家兔同时ⅳ后,采用新建立的溶剂萃取,分光光度法和Carlson法分别测定两药血浆浓度。结果用微机分析拟合曲线,符合二室开放模型。两药联合应用后,烟酸T_1/2β(2.3374 h)和AUC(361.63μg·h/ml)较单用炳酸时T_1/2β(0.9846h)和AUC(157.71μg·h/ml),差异非常显著(P<0.01)。其它参数在两种情况下均无显著差别。     

吡喹酮对感染日本血吸虫小鼠与家兔的疗效和血药浓度的关系

本文报道小鼠与家兔感染日本血吸虫后不同时间用吡喹酮ig或im治疗,其疗效与周用血药浓度无密切的平行关系。在疗效相仿的剂量下,感染4wk鼠给药后的最高血药浓度达20.2μg/ml,而感染 4wk兔的血药浓度仅为0.05μg/ml。从感染兔的十二指肠注人吡喹酮时,则门静脉的血药浓度最高可达15～25μg/ml。结果显示感染宿主ig吡喹酮治疗时,门静脉的血药浓度可能在吡喹酮杀虫过程中具有重要意义。     

Felbamate pharmacokinetics in the rat, rabbit, and dog.

Rats, rabbits, and dogs were given single iv or single and multiple oral doses of felbamate ranging from 1.6-1000 mg/kg. Absorption of oral drug was complete in all species. The mean Cmax increased with dose from 13.9 to 185.9 micrograms/ml in rats, from 19.1 to 161.9 micrograms/ml in rabbits, and from 12.6 to 168.4 micrograms/ml in dogs. The tmax also increased with dose from 1-8 hr in rats, 8-24 hr in rabbits, and 3-7 hr in dogs. The plasma elimination half-life for the drug increased with dose from 2-16.7 hr in rats, 7.2-17.8 hr in rabbits, and 4.1-4.5 hr in dogs. A proportional increase in Cmax with dose was observed in all species up to 300-400 mg/kg doses. A biexponential equation fitted the drug plasma concentration vs. time data well. For multiple oral doses of 50 mg/kg or less, projected and observed steady-state concentrations agreed well. Animals dosed with [14C]felbamate eliminated most of the radioactivity in urine (58-87.7%), less in feces (7-23.7%), with considerable amounts in the bile. In rats, radioactivity was readily distributed into tissues and crossed the placenta and blood-brain barrier, but no accumulation in any tissue was observed. The volume of distribution was 131, 54, and 72% of body weight for rats, rabbits, and dogs, respectively. Binding of drug to rat, rabbit, and dog plasma proteins ranged from 22.4-35.9%. The overall plasma clearance of the drug for rats, rabbits, and dogs was 327, 52, and 108 ml.h-1.kg-1, respectively. Renal clearance of unchanged drug accounted for an estimated 20-35% and hepatic clearance due to metabolism for 65-80% of the overall clearance.