Casulli Adriano, Morales Maria Angeles Gomez, Gallinella Bruno, Turchetto Luciana, Pozio Edoardo
Department of Infectious, Parasitic and Immunomediated Diseases Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
J Antimicrob Chemother. 2006 Oct;58(4):886-90. doi: 10.1093/jac/dkl329. Epub 2006 Aug 8.
We evaluated whether the effectiveness of albendazole against encapsulated larvae increases when 2-hydroxypropyl-beta-cyclodextrin (HP-betaCD) is added to improve bioavailability.
Mice were infected with Trichinella spiralis and treated with albendazole alone, albendazole plus HP-betaCD or not at all (controls) (Experiment I). Both immediately after treatment [76 days post-infection (p.i.)] and later (139 days p.i.) larvae were recovered, and the mean count was expressed in proportion to the larva count for controls. To evaluate the infectivity of the recovered larvae, the larvae recovered at 76 days p.i. and 139 days p.i. were used to infect another three groups (Experiments II and III, respectively).
At 76 days p.i., the percentage of larvae recovered was 77.4% for mice treated with albendazole alone and 61.2% for those treated with albendazole plus HP-betaCD; at 139 days p.i., these percentages were 67.4% and 40.9%, respectively (Experiment I). In Experiments II and III, the percentage of larvae collected from the albendazole group and the combined-treatment group was 55.2% and 27.6%, and 53.1% and 26.6%, respectively. The ABZSO active metabolite was analysed to determine the bioavailability of albendazole. For the combined-treatment group, the area under the plasma concentration-time curve between 0 and 6 h was higher than that for the albendazole group.
These data suggest that HP-betaCD increases the bioavailability and consequently the effectiveness of albendazole against encapsulated Trichinella larvae.
我们评估了添加2-羟丙基-β-环糊精(HP-βCD)以提高生物利用度时,阿苯达唑对包囊幼虫的有效性是否会增加。
用旋毛虫感染小鼠,并分别用阿苯达唑单独治疗、阿苯达唑加HP-βCD治疗或不治疗(对照组)(实验I)。在治疗后立即(感染后76天)和之后(感染后139天)收集幼虫,并将平均计数表示为与对照组幼虫计数的比例。为了评估回收幼虫的感染性,分别使用在感染后76天和139天回收的幼虫感染另外三组(分别为实验II和III)。
在感染后76天,单独用阿苯达唑治疗的小鼠回收幼虫的百分比为77.4%,用阿苯达唑加HP-βCD治疗的小鼠为61.2%;在感染后139天,这些百分比分别为67.4%和40.9%(实验I)。在实验II和III中,从阿苯达唑组和联合治疗组收集的幼虫百分比分别为55.2%和27.6%,以及53.1%和26.6%。分析阿苯达唑亚砜(ABZSO)活性代谢物以确定阿苯达唑的生物利用度。对于联合治疗组,0至6小时血浆浓度-时间曲线下面积高于阿苯达唑组。
这些数据表明,HP-βCD提高了生物利用度,从而提高了阿苯达唑对包囊旋毛虫幼虫的有效性。