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首页> 外文期刊>Clinical therapeutics >Assessment of the bioequivalence of two formulations of clarithromycin extended-release 500-mg tablets under fasting and fed conditions: a single-dose, randomized, open-label, two-period, two-way crossover study in healthy Jordanian male volunteers.
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Assessment of the bioequivalence of two formulations of clarithromycin extended-release 500-mg tablets under fasting and fed conditions: a single-dose, randomized, open-label, two-period, two-way crossover study in healthy Jordanian male volunteers.

机译：在禁食和进食条件下评估两种制剂克拉霉素500毫克缓释制剂的生物等效性：在约旦健康的男性志愿者中进行的单剂量，随机，开放标签，两期，双向转换研究。

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BACKGROUND: Clarithromycin extended-release tablets are indicated for the treatment of adults with acute maxillary sinusitis caused by Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae; acute bacterial exacerbation of chronic bronchitis due to H influenzae, Haemophilus parainfluenzae, M catarrhalis, or S pneumoniae; or community acquired pneumonia due to H influenzae, H parainfluenzae, M catarrhalis, S pneumoniae, Chlamydia pneumoniae, or Mycoplasma pneumoniae. OBJECTIVE: This study was conducted to assess the bioequivalence of test and reference formulations of clarithromycin extended-release 500-mg tablets under fasting and fed conditions. METHODS: This was a single-dose, randomized, open-label, 2-period, 2-way crossover study with a 1-week washout period between doses. Separate bioequivalence studies (fasting and fed) were performed in 2 groups of healthy male Jordanian volunteers. Eighteen blood samples were obtained from each volunteer over 38 hours after drug administration. Clarithromycin concentrations were determined in plasma using a validated high-performance liquid chromatography method with electrochemical detection. Pharmacokinetic parameters of clarithromycin (C(max), T(max), AUC(0-t), AUC(0-infinity), lambda(z) [first-order elimination rate constant], and t((1/2))) were calculated and analyzed statistically. Tolerability was assessed based on changes in vital signs and laboratory tests, and by questioning subjects about adverse events. RESULTS: Thirty-eight volunteers each participated in the fasting and fed studies. The mean ages of participants in the fasting and fed studies were 26.7 and 27.6 years, respectively; their mean weight was 71.2 and 70.9 kg and mean height was 171.3 and 179.0 cm. Under fasting conditions, the arithmetic mean (SD) C(max) was 569.4 (189.3) ng/mL for the test formulation and 641.2 (202.0) ng/mL for the reference formulation, with a geometric mean ratio of 0.88. The arithmetic mean AUC(0-t) was 8602.9 (4105.1) and 8245.3 (4122.4) ng . h/mL in the respective formulations, with a geometric mean ratio of 1.06. The arithmetic mean T(max) was 8.0 (5.6) and 6.1 (3.8) hours. In the fed study, the C(max) and AUC of both formulations were significantly increased relative to the fasting study (P < 0.05). The arithmetic mean C(max) of the 2 formulations was 1183.0 (637.5) and 1199.6 (496.3) ng/mL, with a geometric mean ratio of 0.93. The arithmetic mean AUC(0-t) was 12,981.2 (7849.0) and 11,822.9 (5790.2) ng . h/mL, with a geometric mean ratio of 1.06. The arithmetic mean T(max) was 5.7 (2.8) and 6.7 (2.5) hours. The 90% CI for the ratio (test:reference) of log-transformed C(max) and AUC values was within the acceptance range of 0.80 to 1.25. The 2 formulations were both well tolerated, and no adverse events were reported during the study. CONCLUSIONS: In these fasting and fed studies in healthy male Jordanian volunteers, the 2 formulations of clarithromycin extended-release 500-mg tablets were found to be bioequivalent according to theUS Food and Drug Administration regulatory definition. Administration with food significantly increased the rate and extent of absorption of both products, with no significant effect on their bioequivalence.
机译：背景：克拉霉素缓释片适用于治疗由流感嗜血杆菌，卡他莫拉菌或肺炎链球菌引起的急性上颌窦炎的成年人。由H流感，副流感嗜血杆菌，卡他性M或肺炎链球菌引起的慢性支气管炎的急性细菌急性发作;或因流感嗜血杆菌，副流感嗜血杆菌，粘膜炎莫拉氏菌，肺炎链球菌，肺炎衣原体或肺炎支原体引起的社区获得性肺炎。目的：本研究旨在评估禁食和进食条件下克拉霉素缓释500毫克片剂的测试和参考制剂的生物等效性。方法：这是一项单剂量，随机，开放标签，2周期，2交叉研究，每次给药之间有1周的洗脱期。在两组健康的约旦男性志愿者中分别进行了生物等效性研究（禁食和进食）。给药后38小时内，从每个志愿者那里采集了18个血液样本。使用经过验证的高效液相色谱法和电化学检测方法测定血浆中克拉霉素的浓度。克拉霉素的药代动力学参数（C（max），T（max），AUC（0-t），AUC（0-infinity），lambda（z）[一阶消除速率常数]和t（（1/2） ））进行统计分析。根据生命体征和实验室检查的变化，并向受试者询问不良事件，评估耐受性。结果：38名志愿者分别参加了禁食和进食的研究。禁食和进食研究的平均年龄分别为26.7岁和27.6岁。他们的平均体重为71.2和70.9公斤，平均身高为171.3和179.0厘米。在禁食条件下，测试制剂的算术平均值（SD）C（max）为569.4（189.3）ng / mL，参考制剂的算术平均值（SD）C（max）为641.2（202.0）ng / mL，几何平均比为0.88。算术平均值AUC（0-t）为8602.9（4105.1）和8245.3（4122.4）ng。各自配方中的h / mL，几何平均比率为1.06。算术平均T（max）为8.0（5.6）和6.1（3.8）小时。在进食研究中，相对于禁食研究，两种配方的C（max）和AUC均显着增加（P <0.05）。 2种配方的算术平均C（max）为1183.0（637.5）和1199.6（496.3）ng / mL，几何平均比为0.93。算术平均AUC（0-t）为12,981.2（7849.0）和11,822.9（5790.2）ng。 h / mL，几何平均比率为1.06。算术平均T（max）为5.7（2.8）和6.7（2.5）小时。对数转换后的C（max）和AUC值之比（测试：参考）的90％CI在0.80至1.25的接受范围内。两种制剂均具有良好的耐受性，并且在研究期间未报告不良事件。结论：在对健康的约旦男性志愿者的禁食和进食研究中，根据美国食品和药物管理局的法规定义，发现2种克拉霉素缓释500毫克制剂具有生物等效性。与食物一起给药显着提高了两种产品的吸收速率和吸收程度，而对它们的生物等效性没有显着影响。

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