硝唑尼特对单剂量华法林药代动力学和药效学的影响。

Effects of nitazoxanide on pharmacokinetics and pharmacodynamics of a single dose of warfarin.

作者信息

Vets Eva, Rossignol Jean-Francois, Jackson Anthony Shane

机构信息

SGS Biopharma Research Unit, Stuivenbert, Antwerp, Belgium.

出版信息

Am J Health Syst Pharm. 2009 May 1;66(9):838-42. doi: 10.2146/ajhp080332.

DOI:10.2146/ajhp080332

PMID:19386947

Abstract

PURPOSE

The effects of nitazoxanide on warfarin pharmacokinetics and pharmacodynamics are examined.

METHODS

This was a Phase I, single-center, open-label, randomized, two-way, crossover study. Secondary endpoints included an evaluation of the effect of nitazoxanide on coagulation parameters observed after a single dose of warfarin and an assessment of the overall tolerability of study treatments. Fourteen healthy men were selected for the study. The study consisted of two treatment periods (Treatment A and Treatment B), each lasting 6 days, with a washout period of at least 21 days between both warfarin intakes. All subjects were scheduled to receive both Treatment A and Treatment B, according to the randomization list. Treatment A consisted of a single oral dose of 25 mg warfarin sodium (five 5-mg tablets). Treatment B consisted of a single oral intake of 25 mg warfarin sodium (five 5-mg tablets) and one 500-mg tablet of nitazoxanide (with nitazoxanide 500 mg continued twice daily for up to 6 days).

RESULTS

All 14 subjects received Treatment B, and 13 of the 14 subjects received Treatment A. Pharmacokinetic results were similar in both treatments, and pharmacodynamic parameters were similar in both treatments. Fourteen adverse events occurred in eight subjects after administration of at least one dose of the study drug. Eleven adverse events occurred in six subjects after treatment with warfarin and nitazoxanide, and three adverse events occurred in two subjects after treatment with warfarin alone. At discharge, a high hemoglobin level and a low total bilirubin level were reported in both groups.

CONCLUSION

Coadministration of nitazoxanide twice daily for six days did not affect the pharmacokinetic or pharmacodynamic properties of a single 25-mg dose of warfarin sodium. Administration of a single dose of warfarin or combined administration of a single dose of warfarin and multiple doses of nitazoxanide appeared safe and well tolerated.

摘要

目的

研究硝唑尼特对华法林药代动力学和药效学的影响。

方法

这是一项I期、单中心、开放标签、随机、双向、交叉研究。次要终点包括评估硝唑尼特对单剂量华法林后观察到的凝血参数的影响，以及评估研究治疗的总体耐受性。选择14名健康男性参与研究。该研究包括两个治疗期（治疗A和治疗B），每个治疗期持续6天，两次华法林给药之间的洗脱期至少为21天。根据随机分组列表，所有受试者均计划接受治疗A和治疗B。治疗A包括单次口服25mg华法林钠（五片5mg片剂）。治疗B包括单次口服25mg华法林钠（五片5mg片剂）和一片500mg硝唑尼特片剂（硝唑尼特500mg持续每日两次，最多6天）。

结果

所有14名受试者接受了治疗B，14名受试者中的13名接受了治疗A。两种治疗的药代动力学结果相似，两种治疗的药效学参数也相似。在至少服用一剂研究药物后，8名受试者发生了14起不良事件。华法林和硝唑尼特治疗后，6名受试者发生了11起不良事件，单独使用华法林治疗后，2名受试者发生了3起不良事件。出院时，两组均报告血红蛋白水平高和总胆红素水平低。