Ruiz-Olmedo María Isabel, González-Hernández Iliana, Palomares-Alonso Francisca, Franco-Pérez Javier, González F María de Lourdes, Jung-Cook Helgi
Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Laboratorio de Neuropsicofarmacología, Instituto Nacional de Neurología y Neurocirugía, Mexico City 14269, Mexico.
Saudi Pharm J. 2017 Mar;25(3):413-418. doi: 10.1016/j.jsps.2016.09.005. Epub 2016 Sep 30.
Although albendazole is the drug-of-choice for the treatment of neurocysticercosis, its efficacy is limited due to its low bioavailability. An alternative for optimizing pharmacological treatment is through drug combinations. studies have shown that nitazoxanide and tizoxanide (the active metabolite of nitazoxanide) exhibit cysticidal activity and that the combination of tizoxanide with albendazole sulfoxide (the active metabolite of albendazole) produced an additive effect. (1) To assess the concentration profile of tizoxanide in plasma and in cerebrospinal fluid; and (2) to evaluate the influence of nitazoxanide on the pharmacokinetics of albendazole in plasma and in cerebrospinal fluid. Two different studies were conducted. In study 1, 10 male Sprague-Dawley rats received a single oral dose of 7.5 mg/kg of nitazoxanide and serial blood and cerebrospinal fluid samples were collected over a period of 4 h. In study 2, 38 healthy male Sprague-Dawley rats were randomly divided into two groups: one of these received a single dose of albendazole (15 mg/kg) and, in the other group, albendazole (15 mg/kg) was co-administered with nitazoxanide (7.5 mg/kg). Plasma and cerebrospinal fluid samples were collected from 0 to 16 h after administration. Albendazole sulfoxide and tizoxanide levels were assayed by using HPLC or LC/MS techniques. In study 1, tizoxanide reached a maximum plasma concentration of 244.42 ± 31.98 ng/mL at 0.25 h; however, in cerebrospinal fluid, this could be detected only at 0.5 h, and levels were below the quantification limit (10 ng/mL). These data indicate low permeation of tizoxanide into the blood brain barrier. In study 2, Cmax, the area under the curve, and the mean residence time of albendazole sulfoxide in plasma and cerebrospinal fluid were not affected by co-administration with nitazoxanide. The results of the present study indicate that in rats at the applied doses, tizoxanide does not permeate into the cerebrospinal fluid. Furthermore, nitazoxanide does not appear to alter significantly the pharmacokinetics of albendazole in plasma or in cerebrospinal fluid.
尽管阿苯达唑是治疗神经囊尾蚴病的首选药物，但其生物利用度低，疗效有限。优化药物治疗的一种替代方法是联合用药。研究表明，硝唑尼特和替唑尼特（硝唑尼特的活性代谢产物）具有杀囊活性，替唑尼特与阿苯达唑亚砜（阿苯达唑的活性代谢产物）联合使用产生了相加作用。（1）评估替唑尼特在血浆和脑脊液中的浓度分布；（2）评估硝唑尼特对阿苯达唑在血浆和脑脊液中药物动力学的影响。进行了两项不同的研究。在研究1中，10只雄性斯普拉格-道利大鼠单次口服7.5mg/kg硝唑尼特，并在4小时内采集系列血液和脑脊液样本。在研究2中，38只健康雄性斯普拉格-道利大鼠随机分为两组：一组单次给予阿苯达唑（15mg/kg），另一组阿苯达唑（15mg/kg）与硝唑尼特（7.5mg/kg）联合给药。给药后0至16小时采集血浆和脑脊液样本。采用高效液相色谱法或液相色谱/质谱技术测定阿苯达唑亚砜和替唑尼特水平。在研究1中，替唑尼特在0.25小时达到最大血浆浓度244.42±31.98ng/mL；然而，在脑脊液中，仅在0.5小时可检测到，且水平低于定量限（10ng/mL）。这些数据表明替唑尼特向血脑屏障的渗透较低。在研究2中，阿苯达唑亚砜在血浆和脑脊液中的Cmax、曲线下面积和平均驻留时间不受与硝唑尼特联合给药的影响。本研究结果表明，在所应用剂量下，替唑尼特在大鼠中不会渗透到脑脊液中。此外，硝唑尼特似乎不会显著改变阿苯达唑在血浆或脑脊液中的药物动力学。
