Mottier M L, Alvarez L I, Pis M A, Lanusse C E
Laboratorio de Farmacología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Pcia. de Buenos Aires, Pje. Arroyo Seco, Campus Universitario, Tandil 7000, Buenos Aries, Argentina.
Exp Parasitol. 2003 Jan-Feb;103(1-2):1-7. doi: 10.1016/s0014-4894(03)00060-2.
The experiments described here report on the correlation between the ex vivo diffusion of different benzimidazole (BZD) anthelmintics into the cestode parasite Moniezia benedeni, and their octanol-water partition coefficients (P.C.). The characterisation of the drug diffusion process into target parasites is relevant to understand the mechanism of drug penetration and the pharmacological activity of anthelmintic drugs. Specimens of the tapeworm M. benedeni, used as a helminth parasite model, were obtained from untreated cattle killed at the local abattoir. The collected parasites were incubated (5-210 min) with either fenbendazole (FBZ), albendazole (ABZ), ricobendazole (RBZ), oxfendazole (OFZ), mebendazole (MBZ), oxibendazole (OBZ), or thiabendazole (TBZ), in a Kreb's Ringer Tris buffer medium at a final concentration of 5 nmol/ml. After the incubation time elapsed, samples of parasite material were chemically extracted and prepared for high performance liquid chromatography (HPLC) analysis to measure drug/metabolite concentrations. Additionally, the octanol-water P.C. for each molecule was estimated as an indicator of drug lipophilicity, using reversed phase HPLC analysis. All the incubated drugs were recovered from the tapeworms as early as 5 min post incubation. There was a high correlation (r=0.87) between drug lipophilicity, expressed as octanol-water P.C. (Log P), and drug availability within the parasite. The most lipophilic BZD compounds (FBZ, ABZ, and MBZ), with P.C. values higher than 3.7, were measured at significative higher concentrations within the tapeworm compared to those drugs with the lowest P.C. values. Considering the results from the current and previous studies, it is clear that passive diffusion is a major mechanism of BZD penetration into cestode parasites, where lipid solubility is a determinant factor influencing the diffusion of these anthelmintic molecules through the parasite tegument.
此处所描述的实验报告了不同苯并咪唑（BZD）驱虫药在体外向绦虫寄生虫贝氏莫尼茨绦虫（Moniezia benedeni）扩散与其正辛醇 - 水分配系数（P.C.）之间的相关性。了解药物向目标寄生虫的扩散过程对于理解药物渗透机制和驱虫药的药理活性至关重要。作为蠕虫寄生虫模型的贝氏莫尼茨绦虫标本，取自当地屠宰场宰杀的未经处理的牛。将收集到的寄生虫在Kreb's Ringer Tris缓冲介质中与芬苯达唑（FBZ）、阿苯达唑（ABZ）、利苯达唑（RBZ）、奥芬达唑（OFZ）、甲苯达唑（MBZ）、奥昔达唑（OBZ）或噻苯达唑（TBZ）孵育（5 - 210分钟），终浓度为5 nmol/ml。孵育时间结束后，对寄生虫材料样本进行化学提取，并制备用于高效液相色谱（HPLC）分析，以测量药物/代谢物浓度。此外，使用反相HPLC分析估计每个分子的正辛醇 - 水P.C.，作为药物亲脂性的指标。所有孵育的药物在孵育后5分钟就最早从绦虫中回收。以正辛醇 - 水P.C.（Log P）表示的药物亲脂性与寄生虫体内药物可用性之间存在高度相关性（r = 0.87）。与P.C.值最低的药物相比，P.C.值高于3.7的亲脂性最强的BZD化合物（FBZ、ABZ和MBZ）在绦虫体内的测量浓度显著更高。考虑到当前和先前研究的结果，很明显被动扩散是BZD渗透到绦虫寄生虫中的主要机制，其中脂溶性是影响这些驱虫分子通过寄生虫皮层扩散的决定性因素。
