阿苯达唑在人体内的药代动力学研究

健康志愿者6人,单剂口服阿苯达唑20mg/kg,用反相高效液相色谱法检测血浆药物浓度。此外监测13例华支睾吸虫病人连续服药6天后的血浆药物浓度。固定相为YWG ODSC_(18)-250×4.6mm,流动相为甲醇-水-冰醋酸(70:30:0.45),紫外检测波长292nm,流速1.0ml,浓度在0.0625-2.0μg/ml之间,药物标准曲线线性关系良好(r=0.9995-0.9998)。单剂口服阿苯达唑20mg/kg后,亚砜及砜的体内过程符合一室模型。其T_(max)分别为4.89h、4.13h;C_(max)分别为0.52μg/ml,0.14μg/ml;T_(1/2Ka)分别为2.14h、1.75h;T_(1/2Ke)分别为6.20h、5.33h。所有标本测定结果,血浆中以亚砜为主,原药及砜的浓度甚低,个体间血药浓度差异较大。     

口服阿苯达唑脂质体治疗沙鼠骨细粒棘球蚴病的实验研究

目的通过动物实验来验证口服阿苯达唑脂质体对骨包虫病的疗效。方法将20只已确认感染骨细粒棘球蚴的子午沙鼠随机分成4组,每组5只,A组为对照组,B、C、D 3组为给药组,给药组采用阿苯达唑脂质体混悬液经口灌胃100 mg/kg.d,连续治疗3个月,分别于30、609、0 d处死给药组动物,测定血液和包虫囊液中的药物及其代谢产物的浓度,于90 d处死对照组动物;对骨包虫病变进行大体及镜下观察;取完整肝脏和肾脏,制备光镜病理切片进行观察。结果经口灌胃连续治疗30 d后,血液中的平均药物浓度及囊内药物浓度基本稳定,统计分析血液中的平均药物浓度和囊内药物浓度差异,有统计学意义(P<0.05),30、60、90 d之间无统计学差异(P>0.05),囊内平均药物浓度(平均为0.494 mg/L)为血药浓度(平均为5.023 mg/L)的1/10。骨包虫囊继续生长,囊肿表面光滑,色清亮,张力高,形态正常,病理切片观察包虫囊生发层和角质层无改变。但角质层偶有钙化。实验动物的肝脏和肾脏无病理形态改变。实验期内未观察到阿苯哒唑脂质体药物本身有明显不良作用。结论口服阿苯达唑脂质体对骨包虫病没有明确治疗效果。     

阿苯达唑脂质体和阿苯达唑片治疗囊型包虫病的临床疗效及安全性

目的 观察阿苯达唑脂质体(L-ABZ)和阿苯达唑片(T-ABZ)治疗囊型包虫病的临床疗效及安伞性.方法 收集1998-2008年我院门诊收治及下乡现场普查发现的囊型包虫病患者269例,采用回顾性病例对照方法,纳入符合病例218例,其中经L-ABZ治疗的患者110例,经T-ABZ治疗的患者108例.依据随访的临床症状及影像和血清学化验结果对比分析药物的疗效及不良反应.短期为服药3个月,长期为服药6个月.囊型包虫病患者分为单囊型(CE1)、多子囊型(CE2)和内囊塌陷坏死型并囊内可见活性子囊(CE3).用χ2检验分析计量资料、计数资料;用Wilcoxon秩和检验分析等级资料;统计学检验均为双侧检验,统计数据均用SPSS13.0及PEMS3.1医学统计软件分析完成.结果 短期疗效评价中,L-ABZ组与T-ABZ组总有效率及治愈率分别为77.9%和49.1%,28.4%和13.9%,两组比较,χ2值分别为19.581、6.877,P值均<0.05,差异有统计学意义.长期疗效评价中,L-ABZ组与T-ABZ组总有效率及治愈率分别为81.7%和49.0%,47.6%和20.6%,两组比较,χ2值分别为20.977、15.049,P值均<0.05,差异有统计学意义.T-ABZ组不同类型包虫囊肿疗效比较:对于短期治愈率、短期总有效率、长期治愈率、长期总有效率,CE1组分别为50.0%(15/30)、56.7%(17/30)、58.3%(7/12)、75.0%(9/12);CE2组分别为8.8%(8/91)、35.2%(32/91)、28.6%(12/42)、69.0%(29/42);CE3组分别为33.3%(7/21)、61.9%(13/21)、70.0%(7/10)、100.0%(10/10).CE1组、CE3组分别与CE2组的短期疗效(治愈率和总有效率)比较,χ2值分别为24.887、4.329、8.860、5.076,P值均<0.05,差异有统计学意义;L-ABZ组不同类型包虫囊肿疗效比较:对于短期治愈率、短期总有效率、长期治愈率、长期总有效率,CE1组分别为47.4%(18/38)、92.1%(35/38)、79.3%(23/29)、96.6%(28/29).CE2组分别为12.2%(12/98)、65.3%(64/98)、35.9%(23/64)、84.40/0(54/64).CE3组分别为61.5%(8/13)、92.3%(12/13)、50.0%(3/6)、100%(6/6).CE1组、CE3组分别与CE2组的短期疗效(治愈率、总有效率)比较,χ2值分别为19.648、9.930、18.880、3.876,P值均<0.05,差异有统计学意义;在安全性评价中,T-ABZ组和L-ABZ组药物相关的不良反应发生率分别为11.1%(12/108)、12.7%(14/110),两组比较,χ2=0.155,P>0.05,差异无统计学意义.结论 L-ABZ及T-ABZ均是有效的抗包虫药物,但L-ABZ临床疗效更佳.

Abstract：

Objective To explore and compare the clinical effect and safety of liposomal albendazole (L-ABZ) and tablet-albendazole (T-ABZ) in the treatment of cystic echinococcosis (CE1, CE2, and CE3). Methods A total of 269 cases treated with cystic echinococcosis (CE) in Xinjiang Medical University the First Affilicated Hospital from 1998 to 2008 were reviewed. 51 cases were excluded and 218 cases were enrolled in this research by retrospective case-control method. Among 110 cases were treated with L-ABZ and 108 cases were treated with T-ABZ for short-term (3 months) and long-term courses (6 months) respectively. The effects and safety of the two medicines were compared by analyzing the clinical symptoms, imaging check and serologic test results. Results In short-term effect evaluation, the total effective rates and curative rates of L-ABZ group and T-ABZ group were 77.9% and 49.1% vs 28.4% and 13.9%, respectively. The effects of L-ABZ group was better than that of T-ABZ group, with remarkable difference in total effective rates and curative rates ( χ2 value was 19.581, 6.877, respectively, P < 0.05). In long-term effect evaluation, the total effective rates and curative rates of L-ABZ and T-ABZ group were 81.7% and 49.0% vs 47.6% and 20.6%, respectively. There was significant difference between L-ABZ group and T-ABZ group in total effective rates and curative rates (χ2 value was 20.977, 15.049, respectively, P < 0.05). In T-ABZ group the short-term curative rates were 50.0% (15/30), 8.8% (8/91) and 33.3% (7/21) respectively in CE1, CE2, and CE3, the short-term total effctive rates were 56.7% (17/30), 35.2% (32/91) and 61.9% (13/21) respectively in CE1, CE2, and CE3. The long-term curative rates were 58.3% (7/12), 28.6% (12/42) and 70.0% (7/10) respectively in CE1, CE2 and CE3, the long-term total effctvie rates were 75.0% (9/12), 69.0% (29/42) and 100.0% (10/10) respectively in CE1, CE2, and CE3. When compared with CE2, differences existed in CE1 ( χ2 = 24.887,4.329; P < 0.05) and CE3 groups ( x 2 = 8.860, 5.076; P < 0.05) in terms of short-term effects. In L-ABZ group, the short-term curative rates were 47.4% (18/38), 12.2% (12/98) and 61.5% (8/13) respectively in CE1, CE2 and CE3, the short-term total effctive rates were 92.1% (35/38), 65.3% (64/98) and 92.3% (12/13) respectively in CE1, CE2 and CE3, the long-term curative rates were 79.3% (23/29), 35.9% (23/64) and 50.0% (3/6) respectively in CE1, CE2 and CE3, the long-term total effective rates were 96.6% (28/29),84.4% (54/64) and 100% (6/6) respectively in CE1, CE2 and CE3. When compared with CE2, there were significant differences in CE1 (χ2 = 19.648, 9.930; P < 0.05) and CE3 groups ( χ2 = 18.880, 3.876; P < 0.05) in terms of short-term effect. In L-ABZ and T-ABZ groups, the durg-related adverse effects were 11.1% (12/108) and 12.7% (14/110) respectively without significant difference ( χ2 = 0.155, P > 0.05). Conclusion L-ABZ and T-ABZ were both effective anti-echinococcosis drugs without dominant sideeffects. The clinical effect of L-ABZ was better than that of T-ABZ.     

用高效液相色谱法测定血浆中的阿苯达唑及其主要代谢物

用高效液相色谱法测定血浆中的阿苯达唑(Alb)及其代谢物阿苯达唑亚砜(AlbSO)和阿苯达唑砜(AlbSP)。检测血浆中的Alb和AlbSO的限度为5ng·ml~(-1),AlbSP的为10ng·ml~(-1)。应用本法检测Alb、AlbSO和AlbSP的回收率均在90％以上。     

阿苯达唑脂质体治疗66例人体包虫病的疗效观察

目的综合评价阿苯达唑脂质体(L-ABZ)治疗人体包虫病的疗效,并进行安全性考察,为该药在临床的应用提供客观依据.方法临床治疗了66例包虫病患者,其中囊型包虫病56例、泡型包虫病10例,口服阿苯达唑脂质体10mg*kg-1*d-1,一天两次,连续服用,疗程3～12个月,通过影像学指标观察,结合临床症状和体征及生化指标进行综合评价,动态随访3～24个月.按治愈率、有效率、部分有效率、无效率以及总有效率判断疗效,并对单囊型及与多子囊型以及原发、复发病人进行对照分析.结果共治愈20例(20/66),治愈率为30.3%;有效29例(29/66),有效率43.9%;部分有效10例(10/66),部分有效率15.1%;无效7例(7/66),无效率10.6%;总有效率为89.3%(59/66).其中,单囊型的治愈率明显高于多子囊型,但二者的有效率无显著性差异(P<0.1);而原发、复发病人的治疗阿苯达唑脂质体的疗效无明显差异(P＞0.1);泡型包虫病患者,约50%病例临床疗效明显.在安全性观察中,主观症状阳性率为13.6%(9/66),生化指标阳性率为12.1%(8/66).结论阿苯达唑脂质体口服液是目前有效的一种抗包虫病新药剂型,具有疗效较高,低毒、副作用小、安全性高的特点.     

阿苯达唑新剂型的药代动力学研究

目的　通过药代动力学研究 ,为选择高效杀棘球蚴药物阿苯达唑 (Albendazole ,ABZ)新剂型提供参考。　方法　选用 2 4只健康Wistar大鼠 ,随机分为 4组 :大分子物 (Macrosol) ABZ(Mac ABZ)组、脂质体 (Liposome) ABZ(L ABZ)组、前体脂质体 (Pre liposome) ABZ(Pre L ABZ)组及片剂ABZ组。按ABZ 5 0mg/kg经口灌药 ,分别于灌药后 1、2、3、4、5、6、7、8、12、2 4、3 6、48h采尾静脉血 ,用HPLC法测定血中ABZ及其代谢产物砜 (ABZSN )和亚砜 (ABZSX )浓度。血药浓度数据用 3P87药代动力学程序软件包分别进行模型嵌合。以Akaie’s信息判断AIC值、回归系数、拟合优度等。用PEMSVer 2 .1统计软件进行显著性检验 ,确定药物在体内的配置状态 ,观察其药代动力学特征。　结果　 1)Pre L ABZ :相对于片剂ABZ ,Pre L ABZ剂型中ABZ的相对生物利用度为 14 6.5 4% (P >0 .0 5 ) ,ABZSX为 2 67.76% (P <0 .0 1) ,ABZSN为 15 5 .2 9% (P <0 .0 1) ;Pre L ABZ的消除速度常数 (β)为 (0 .0 5± 0 .0 2 )l/h ,半衰期 (t1/ 2 β)为 (17.16± 6.48)h ,清除率 (CL)为 (0 .0 6± 0 .0 1)ng/ml。片剂ABZ的 β为 (0 .10± 0 .0 4)l/h ,t1/ 2 β为 (6.60± 2 .0 3 )h ,CL为 (0 .11±0 .0 4)ng/ml ,差异均有显著性 (P <0 .0 5 )。Pre     

Albendazole-soybean oil emulsion for the treatment of human cystic echinococcosis: evaluation of bioavailability and bioequivalence

A single 12.5 mg/kg dose of albendazole (Abz) in tablet form (AbzT) followed 2 weeks later by an equivalent dose of Abz emulsified in 30% soybean oil (AbzE) was administered orally 2 h after the first morning meal to 7 male adult patients with cystic echinococcosis caused by Echinococcus granulosus. Serum samples were taken 1, 3, 5, 7, 8, 9, 11, 14, 18, 24, 36, and 48 h post medication from each patient to measure the serum concentrations of albendazole sulfoxide (AbzSOX), the principal bioactive metabolite of Abz. AbzSOX concentrations were measured by reverse phase HPLC. The data were subjected to pharmacokinetic analysis to compare the relative bioavailability and bioequivalence of AbzT and AbzE. The results demonstrated that the mean peak concentrations (C(max)) for AbzT and AbzE were 1.06+/-0.38 mg/l and 1.71+/-0.47 mg/l, respectively; the area under the concentration-time curves (AUC) were 13.24+/-4.93 mg x h/l and 21.01+/-7.54 mg x h/l, respectively. The relative bioavailability of AbzE was F(Flu)=1.59. Two one-sided tests procedure and (1-2 alpha) 90% confidence interval methods were used to evaluate the bioequivalence of AbzE and AbzT. The results demonstrated that the bioavailability of AbzE was greater than AbzT.     

细粒棘球蚴囊经甲苯达唑、阿苯达唑或阿苯达唑亚砜作用后其生发层的形态学变化和药物含量

小鼠的继发性细粒棘球蚴囊在含甲苯达唑阿苯达唑或阿苯达唑亚枫1及10μg/ml的培养液中培养l～7d时,囊壁所含各药物的量相近,但生发层的受损以甲苯达唑组较重,次为阿苯达唑亚砜和阿苯达唑组。感染小鼠ig上述3种苯并咪唑类化合物的等效剂量1～14d后24h,囊壁的药物含量甚低,但生发层的损害仍以甲苯达唑组的较重,并认为阿苯达唑亚矾是阿苯达唑的有效代谢物。     

Intranasal Administration of Insulin With Phospholipid as Absorption Enhancer: Pharmacokinetics in Normal Subjects

The pharmacokinetics of intranasal insulin containing a medium-chain phospholipid (didecanoyl-L-alpha-phosphatidylcholine) as absorption enhancer, was studied in normal volunteers by measuring plasma glucose, insulin, C-peptide, and glucagon. Eleven fasting subjects received 4 U insulin intravenously, 6 U subcutaneously, or three doses intranasally (approximately 0.3 U kg^?1, 0.6 U kg^?1, 0.8 U kg^?1) in random order on five separate days. Intranasal insulin was absorbed in a dose-dependent manner with a mean plasma insulin peak 23 ± 7 (± SE) min after administration. Mean plasma glucose nadir was seen after 44 ± 6 min, 20 min later than following intravenous injection. Furthermore, intranasal administration of insulin resulted in a faster time-course of absorption than subcutaneous injection, with significantly reduced intersubject variation (p < 0.001). Bioavailability for the nasal formulation was 8.3% relative to an intravenous bolus injection when plasma insulin was corrected for endogenous insulin production estimated by C-peptide. A dose-dependent suppression of C-peptide and stimulation of glucagon secretion occurred after intranasal administration of insulin. Nasal irritation from spraying was absent or slight.     

Role of Albendazole in the Management of Hydatid Cyst Liver

Background/Aim:

Hydatidosis has a worldwide distribution and the liver is the most common organ involved. Hydatid cysts of the liver can be managed either by nonoperative or operative methods. Nonoperative methods include chemotherapy and percutaneous treatment. The study aimed at understanding the effect of albendazole therapy on the viability of protoscoleces and recurrence rate of hydatid disease of the liver.

Patients and Methods:

The study was conducted at Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India, over a period of 2 years from January 2002 to December 2003, with further follow-up of 5 years. The study included 72 cases in the age group of 17-66 years, comprising 39 males and 33 females. The patients were randomized into two groups of 36 patients each. In group A, patients were directly subjected to surgery, while in group B, patients were administered albendazole for 12 weeks preoperatively, followed by a further postoperative course for 12 weeks.

Results:

Of patients who received albendazole therapy, no patient had viable cysts at the time of surgery, as compared to 94.45% of the patients who did not receive any preoperative albendazole (P<0.01). In patients who did not receive any albendazole therapy, recurrence rate was 16.66%, while no recurrence was seen in patients who received albendazole therapy (P≤0.05).

Conclusion:

We conclude that albendazole is an effective adjuvant therapy in the treatment of hydatid liver disease.     

阿苯达唑和吡喹酮联合用药治疗小鼠继发性细粒棘球蚴的研究

本试验采用正交设计，在不同的药物处理，疗程、剂量和感染时间等多种因素作用下，以感染率，囊重（抑制率）、囊数及包虫病理改变为评价指标，观察了联合应用阿苯达唑与吡喹酮治疗小鼠腹腔感染的原头节及包虫囊的效果。结果表明：联合用药无论对感染的原头节还是发育的包虫囊均有明显疗效，优于单一用药，而且在原头节感染早期用药的效果较优，这一结果对临床化疗有一定意义。     

汉防己甲素联合阿苯达唑抑制小鼠棘球蚴生长作用及其机制的研究

为研究中药汉防己甲素单独及联合阿苯达唑用药对小鼠继发性细粒棘球蚴的抑制作用 ,探讨其作用的机制及寻找药物治疗细粒棘球蚴病的新途径。将动物体内实验分成 5组 :阿苯达唑组、汉防己甲素组、汉防己甲素 +阿苯达唑组、对照组和空白组。对小鼠继发性细粒棘球蚴病药物治疗 90d后 ,检测各组小鼠棘球蚴囊湿重、血清IL 2 ,IL 4,IL 12和IgE的含量 ;实验结果显示汉防己甲素单独及联合阿苯达唑均有明显的抑制小鼠棘球蚴生长的作用 (抑囊率分别为 47. 96% ,64 . 86%和 83 . 14 % ) ,其中联合用药明显优于单独用药 (P <0 . 0 5 )。各治疗组中小鼠血清IL 2 ,IL 4,IL 12 ,IgE含量与对照组比较有显著性差异 (P <0 . 0 5 )。因此 ,汉防己甲素和阿苯达唑对小鼠棘球蚴生长均有一定的抑制作用 ,与阿苯达唑联合治疗效果更佳 ,这可能与汉防己甲素可逆转阿苯达唑的抗药性及提高小鼠机体的免疫力有关。联合用药是提高阿苯达唑驱虫效果的有效途径之一。     

已酮可可碱联合阿苯达唑治疗小鼠泡球呦病的疗效观察

目的观察己酮可可碱(PTX)和阿苯达唑(ABZ)单独及联合用药对小鼠继发性泡球蚴病的疗效。方法对小鼠继发性泡球蚴病进行药物治疗,各治疗组药物用量分别为:ABZ组50mg/(kg·d);PTX高剂量组360mg/(kg·d);PTX低剂量组180mg/(kg·d);联合组ABZ50mg/(kg·d) PTX180mg/(kg·d);感染对照组(未治疗组)和空白对照组均给予等体积生理盐水,用小鼠灌胃针经口每天灌胃给药1次,连续治疗100d后(其间14只死亡),检测各小鼠泡球蚴湿重、抑囊率及小鼠血清细胞因子转化生长因子-β(TGF-β)、白细胞介素-2(IL-2)和IL-10;并对泡球蚴组织进行病理组织学和超微结构观察。结果PTX在体外能有效地杀灭原头节(高剂量组为100%),在体内对泡球蚴抑制作用虽较弱(高剂量组为37%),但能增强小鼠的免疫力。联合用药对泡球蚴有明显的抑制作用,抑囊率为88%,ABZ抑囊率为58%(P<0.05)。结论PTX联合ABZ治疗小鼠继发性泡球蚴病疗效明显优于ABZ。     

甲苯达唑、阿苯达唑及其代谢物实验治疗小鼠继发性细粒棘球蚴病的研究

在疗程为10～14d时,甲苯达唑对小鼠继发性细粒棘球蚴病的最低有效剂量为25mg/kg/d,阿苯达唑的为100mg/kg/d。在所用的疗程下,甲苯达唑的剂量较阿笨达唑100～300mg/kg/d低3～11倍时,它们的疗效相仿,但甲苯达唑100mg/kg/d的疗效则优于剂量大l～2倍的阿苯达唑。甲苯达唑与阿苯达唑合并治疗未能明显提高疗效,但此2种药物并用吡喹酮治疗则疗效明显提高。实验证明阿苯达 唑亚砜的疗效优于阿苯达唑,而阿苯达唑用则无效。