Quetglas Emilio García, Campanero Miguel Angel, Sádaba Belén, Escolar Manuel, Azanza Jose Ramón
Clinical Research Unit, Clínica Universitaria de Navarra, Universidad de Navarra, Pamplona, Spain.
Arzneimittelforschung. 2008;58(6):283-7. doi: 10.1055/s-0031-1296508.
Triflusal (CAS 322-79-2) is an antiplatelet agent related to salicylates used in several European and Latin American countries in the treatment of cardiovascular diseases. The aim of this paper was to evaluate the bioequivalence of triflusal derived from two preparations using both parent drug and metabolite pharmacokinetic data. The bioavailabolity was measured in 24 healthy male Caucasian volunteers following a single oral dose (600 mg) of the test or reference products in the fasting state. Blood samples were collected for 120 h. Plasma concentrations of triflusal and its metabolite 3-hydroxy-4-trifluoromethylbenzoic acid (HTB) were analyzed by high-performance liquid chromatography with UV and fluorescence detection, respectively. The non-compartmental method was used for pharmacokinetic analysis. Log-transformed Cmax, AUC0-t and AUC0-infinity were tested for bioequivalence using ANOVA and Schuirmann's two-one sided t-test. Tmax was analyzed by nonparametric pharmacokinetic parameters of triflusal and HTB derived from the two formulations were nearly consistent with previous observations. Triflusal parameters derived from the test and reference drug were as follows: Cmax (16.85 +/- 11.41 vs 14.48 +/- 7.22 mg/l), AUC0-t (18.43 +/- 10.91 vs 16.22 +/- 7.58 mg/l per hour), Tmax (1 range 0.25-2h vs 0.875 range 0.25-1.5 h), and t(1/2) (0.49 +/- 00.27 vs 0.76 +/- 0.64). HTB parameters after test and reference formulation administration were as follows: Cmax (68.13 +/- 23.05 vs 65.51 +/- 19.44 mg/l), AUC0-t (2748.18 +/- 971.91 vs 2877.97 +/- 881.2 h x mg/l), AUC0-infinity (3350.15 +/- 1182.62 vs 3372.49 +/- 1110.35 h x mg/l), Tmax (2 range 1-10 h vs 2 range 0.75-12 h), and t(1/2) (42.19 +/- 7.82 vs 43.13 +/- 6.56 h). 90% of confidence intervals for the test/reference ratio of Cmax AUC0-t and AUC0-infinity derived from both triflusal and HTB were found within the range of 80%-125% acceptable for bioequivalence. No significant difference was found between the Tmax values for triflusal and HTB. It was concluded that the two preparations are bioequivalent and may be prescribed interchangeably.
曲氟柳（CAS 322-79-2）是一种与水杨酸盐相关的抗血小板药物，在欧洲和拉丁美洲的几个国家用于治疗心血管疾病。本文的目的是利用母体药物和代谢物的药代动力学数据，评估两种制剂的曲氟柳生物等效性。在24名健康的白种男性志愿者空腹状态下单次口服剂量（600mg）的受试产品或参比产品后，测定其生物利用度。采集血样120小时。分别采用高效液相色谱-紫外检测法和荧光检测法分析曲氟柳及其代谢物3-羟基-4-三氟甲基苯甲酸（HTB）的血浆浓度。采用非房室模型法进行药代动力学分析。使用方差分析和Schuirmann双单侧t检验对经对数转换的Cmax、AUC0-t和AUC0-∞进行生物等效性检验。采用非参数方法分析Tmax。两种制剂的曲氟柳和HTB的药代动力学参数与先前观察结果基本一致。受试药物和参比药物的曲氟柳参数如下：Cmax（16.85±11.41对14.48±7.22mg/l），AUC0-t（18.43±10.91对16.22±7.58mg/l·小时），Tmax（1范围0.25 - 2小时对0.875范围0.25 - 1.5小时），以及t(1/2)（0.49±0.27对0.76±0.64）。受试制剂和参比制剂给药后的HTB参数如下：Cmax（68.13±23.05对65.51±19.44mg/l），AUC0-t（2748.18±971.91对2877.97±881.2小时·mg/l），AUC0-∞（3350.15±1182.62对3372.49±1110.35小时·mg/l），Tmax（2范围1 - 10小时对2范围0.75 - 12小时），以及t(1/2)（42.19±7.82对43.13±6.56小时）。曲氟柳和HTB的Cmax、AUC0-t和AUC0-∞的试验/参比比值的90%置信区间在生物等效性可接受的80% - 125%范围内。曲氟柳和HTB的Tmax值之间未发现显著差异。结论是这两种制剂具有生物等效性，可以互换处方使用。
