Stockis A, Deroubaix X, Lins R, Jeanbaptiste B, Calderon P, Rossignol J F
Bio-Pharma S.A., Wavre, Belgium.
Int J Clin Pharmacol Ther. 1996 Aug;34(8):349-51.
The objective of this study was to gather first information on the time course of plasma concentrations and urinary excretion of the antiprotozoal nitazoxanide (N) and to identify potential metabolites in healthy subjects after a single oral dose of 500 mg of nitazoxanide. The clinical trial was conducted as an open single oral dose study in 6 healthy male subjects. After a standardized continental breakfast the subjects took a single oral dose of 500 mg nitazoxanide (coated tablet) with 100 ml tap water. The plasma concentration and the urinary excretion of nitazoxanide (N), desacetyl-nitazoxanide (DN), aminonitrothiazole (ANT), acetylsalicylate (AS), salicylate (S), gentisate (G) and salicylurate (SU) were monitored up to 72 h after administration. The only measurable species in plasma was DN, which reached a Cmax of 1.9 mg/l (range 1.1-2.5) 2-6 h after dosing, and an AUC of 3.9-11.3 mg x h/l. Its terminal half-life ranged from 1.03 to 1.6 h. DN was extensively bound to plasma proteins (> 97.5%). Only 8% of the dose was recovered in the urine, in the form of DN (5%), SU (3%), and traces of ANT (0.1%). In vitro N was very rapidly hydrolyzed to DN by plasma esterases.
本研究的目的是获取关于抗原生动物药硝唑尼特（N）的血浆浓度和尿排泄时间过程的初步信息，并确定健康受试者单次口服500 mg硝唑尼特后的潜在代谢产物。该临床试验作为一项开放性单次口服剂量研究，在6名健康男性受试者中进行。在食用标准化的欧式早餐后，受试者用100 ml自来水单次口服500 mg硝唑尼特（包衣片）。在给药后长达72小时内监测硝唑尼特（N）、去乙酰硝唑尼特（DN）、氨基硝基噻唑（ANT）、乙酰水杨酸（AS）、水杨酸（S）、龙胆酸盐（G）和水杨尿酸（SU）的血浆浓度和尿排泄情况。血浆中唯一可测量的物质是DN，给药后2 - 6小时达到最大浓度（Cmax）为1.9 mg/l（范围1.1 - 2.5），曲线下面积（AUC）为3.9 - 11.3 mg·h/l。其末端半衰期为1.03至1.6小时。DN与血浆蛋白广泛结合（> 97.5%）。仅8%的剂量以DN（5%）、SU（3%）和痕量ANT（0.1%）的形式在尿液中回收。在体外，N被血浆酯酶非常迅速地水解为DN。
