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首页> 外文期刊>Clinical therapeutics >Comparison of the pharmacokinetics of ticlopidine between administration of a combined fixed-dose tablet formulation of ticlopidine 250 mg/ginkgo extract 80 mg, and concomitant administration of ticlopidine 250-mg and ginkgo extract 80-mg tablets: an open-label, two-treatment, single-dose, randomized-sequence crossover study in healthy Korean male volunteers.
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Comparison of the pharmacokinetics of ticlopidine between administration of a combined fixed-dose tablet formulation of ticlopidine 250 mg/ginkgo extract 80 mg, and concomitant administration of ticlopidine 250-mg and ginkgo extract 80-mg tablets: an open-label, two-treatment, single-dose, randomized-sequence crossover study in healthy Korean male volunteers.

机译：噻氯匹定的固定剂量片剂250 mg /银杏提取物80 mg的固定剂量组合给药与噻氯匹定250 mg和银杏提取物80 mg片剂的同时给药之间的噻氯匹定的药代动力学比较：开放标签，两次治疗，对健康的韩国男性志愿者进行的单剂量，随机序列交叉研究。

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BACKGROUND: Ticlopidine is an antiplatelet agent used for the prevention of vascular accidents. In clinical practice in Korea, ginkgo extract may be administered along with ticlopidine to enhance the inhibition of platelet aggregation. OBJECTIVE: To meet the requirements for marketing a combined fixed-dose formulation in Korea, the investigators compared the pharmacokinetic characteristics of ticlopidine in a combined fixed-dose tablet of ticlopidine/ginkgo extract with the concomitant administration of ticlopidine and ginkgo extract tablets. METHODS: An open-label, 2-period, 2-treatment, single-dose, randomized-sequence crossover study was conducted in healthy Korean male volunteers. Subjects were randomly allocated to 2 sequence groups. In one period, a combined ticlopidine 250 mg/ ginkgo extract 80-mg fixed-dose tablet was administered and, in the other period, ticlopidine 250-mg and ginkgo extract 80-mg tablets were concomitantly administered. A 7-day washout separated the 2 periods. For analysis of pharmacokinetic properties, including C(max), T(max), t((1/2)), AUC(0-infinity), and AUC(0-last), serial blood sampling was performed up to 48 hours after study drug administration during each period. Ticlopidine concentrations in plasma were determined by a validated method using LC-MS/MS. In order for the 2 treatments to be considered bioequivalent, the 90% CI of the geometric means ratios for C(max) and AUC needed to be between 80% and 125%. Bleeding time was determined before dosing (0 hour) and at 5 and 24 hours after dosing. Adverse events (AEs) were identified through patient interview, recording of blood pressure, heart rate, and body temperature, physical examination, 12-lead ECG, and laboratory assessments. RESULTS: Twenty-four healthy Korean male subjects (mean [range] age, 23.9 [22-38] years; height, 174.0 [162-184] cm; weight, 67.4 [56-80] kg) completed the study. Median (range) T(max) of ticlopidine was 1.5 (0.5-2.0) hours in both groups. The mean (SD) t((1/2)) of ticlopidine in the combined fixed-dose formulation and the concomitant administration groups was 19.5 (3.4) and 19.0 (3.3) hours after study drug administration, respectively. The geometric means ratios of ticlopidine AUC(0-last), AUC(0-infinity), and C(max) between the combined fixed-dose formulation and concomitant administration were 1.04 (90% CI, 0.96-1.13), 1.04 (90% CI, 0.96-1.13), and 1.09 (90% CI, 0.96-1.23), respectively. The mean (SD) bleeding time at predose (0), and 5 and 24 hours after dose administration was 4.5 (1.6) to 5.4 (1.7) minutes in the combined fixed-dose formulation group and 4.4 (1.6) to 5.1 (1.1) minutes in the concomitant administration group. Five subjects (3 in the combined fixed-dose formulation group and 2 in the concomitant administration group) had bleeding times >8 minutes, but this was not considered to be clinically significant. A total of 24 AEs were reported in 13 of 24 subjects: nausea (3 cases), diarrhea (3), dizziness (3), epigastric discomfort (2), headache (2), rhinorrhea (2), purulent sputum (2), dyspepsia (1), upper abdominal pain (1), cough (1), pharyngolaryngeal pain (1), oropharyngeal swelling (1), dysphonia (1), and dysphagia (1). All were considered mild or moderate in nature. There was no statistically significant difference between the 2 treatments in the number of AEs or in the number of subjects who reported an AE. CONCLUSION: Administration of a single dose of a combined fixed-dose formulation of ticlopidine 250 mg/ ginkgo extract 80-mg tablets and concomitant administration of ticlopidine and ginkgo extract tablets did not result in statistically significant differences in the pharmacokinetics of ticlopidine in these healthy Korean male volunteers.
机译：背景：噻氯匹定是一种用于预防血管意外的抗血小板药。在韩国的临床实践中，可以将银杏提取物与噻氯匹定一起服用，以增强对血小板聚集的抑制作用。目的：为了满足在韩国销售固定剂量联合制剂的要求，研究人员比较了噻氯匹定/银杏提取物固定剂量片剂与噻氯匹定和银杏提取物片剂同时给药的噻氯匹定的药代动力学特征。方法：在健康的韩国男性志愿者中进行了开放标签，2周期，2治疗，单剂量，随机序列交叉研究。将受试者随机分配至2个序列组。在一个时期中，联合使用噻氯匹定250 mg /银杏提取物80 mg固定剂量片剂，在另一时期中，同时施用噻氯匹定250 mg /银杏提取物80 mg片剂。为期7天的冲销将2个期间分开。为了分析包括C（max），T（max），t（（1/2）），AUC（0-infinity）和AUC（0-last）在内的药代动力学特性，进行了长达48小时的连续血液采样在每个时期研究药物给药后。血浆中噻氯匹定的浓度采用LC-MS / MS通过验证方法确定。为了使这两种处理方法具有生物等效性，C（max）和AUC的几何均数比的90％CI必须在80％和125％之间。在给药前（0小时）以及给药后5和24小时确定出血时间。通过患者访谈，记录血压，心率和体温，体格检查，12导联心电图和实验室评估来确定不良事件（AE）。结果：二十四名健康的韩国男性受试者（平均年龄23.9 [22-38]岁;身高174.0 [162-184] cm;体重67.4 [56-80] kg）完成了研究。两组中噻氯匹定的中位（范围）T（最大值）为1.5（0.5-2.0）小时。联合固定剂量制剂和同时给药组中噻氯匹定的平均（SD）t（（1/2））分别为研究药物给药后19.5（3.4）和19.0（3.3）小时。固定剂量组合制剂与同时给药之间的噻氯匹定AUC（0-last），AUC（0-infinity）和C（max）的几何平均值之比为1.04（90％CI，0.96-1.13），1.04（90 CI分别为0.96-1.13）和1.09（90％CI为0.96-1.23）。在固定剂量联合制剂组中，在给药前（0）以及给药后5和24小时的平均（SD）出血时间为4.5（1.6）至5.4（1.7）分钟，而4.4（1.6）至5.1（1.1）会议同时进行的会议记录。五名受试者（固定剂量联合制剂组中的3名，并用给药组中的2名）的出血时间大于8分钟，但是这在临床上不具有显着意义。在24名受试者中的13名受试者中报告了总共24例AE：恶心（3例），腹泻（3），头晕（3），上腹不适（2），头痛（2），鼻漏（2），化脓性痰（2） ，消化不良（1），上腹痛（1），咳嗽（1），咽喉痛（1），口咽部肿胀（1），声音障碍（1）和吞咽困难（1）。所有这些人本质上都被视为轻度或中度。两种治疗之间的AE数量或报告AE的受试者数量在统计学上无显着差异。结论：在这些健康的韩国人中，单剂量联合固定剂量噻氯匹定250 mg /银杏提取物80 mg片的给药以及噻氯匹定和银杏提取物片剂的同时给药并未导致噻氯匹定的药代动力学统计学上显着差异男志愿者。

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