Khandave Suhas S, Sawant Satish V, Joshi Santosh S, Bansal Yatish K, Kadam Sonal S
Accutest Research Laboratories (I), Private Limited, Koparkhirne, Navi Mumbai, Maharashtra, India.
Drug Des Devel Ther. 2010 Nov 25;4:367-74. doi: 10.2147/DDDT.S15133.
Tramadol hydrochloride is available as 50 mg immediate-release (IR) and 100 mg, 200 mg, and 300 mg sustained-release (SR) tablets. The recommended dose of tramadol is 50-100 mg IR tablets every 4-6 hours. The tramadol SR 200 mg tablet is a better therapeutic option, with a reduced frequency of dosing, and improved patient compliance and quality of life. The present study evaluated the bioequivalence of a generic tramadol SR 200 mg tablet.
A comparative in vitro dissolution study was performed on the test and reference products, followed by two separate single-dose bioequivalence studies under fasting and fed conditions and one multiple-dose bioequivalence study under fasting conditions. These bioequivalence studies were conducted in healthy human subjects using an open-label, randomized, two-treatment, two-period, two-sequence, crossover design. The oral administration of the test and reference products was done on day 1 for both the single-dose studies and on days 1-5 for the multiple-dose study in each study period as per the randomization code. Serial blood samples were collected at predefined time points in all the studies. Analysis of plasma concentrations of tramadol and O-desmethyltramadol (the M₁ metabolite) was done by a validated liquid chromatography-mass spectrometry analytical method. The standard acceptance criterion of bioequivalence was applied on log-transformed pharmacokinetic parameters for tramadol and its M₁ metabolite.
The ratios for geometric least-square means and 90% confidence intervals were within the acceptance range of 80%-125% for log-transformed primary pharmacokinetic parameters for tramadol and its M₁ metabolite in all the three studies.
The test product is bioequivalent to the reference product in terms of rate and extent of absorption, as evident from the single-dose and multiple-dose studies. Both the treatments were well tolerated.
盐酸曲马多有50毫克速释（IR）片剂以及100毫克、200毫克和300毫克缓释（SR）片剂。曲马多的推荐剂量为每4 - 6小时服用50 - 100毫克IR片剂。200毫克曲马多SR片剂是更好的治疗选择，给药频率降低，患者依从性和生活质量得到改善。本研究评估了一种200毫克曲马多SR仿制药片的生物等效性。
对受试产品和参比产品进行了体外溶出度对比研究，随后在空腹和进食条件下分别进行了两项单剂量生物等效性研究，以及在空腹条件下进行了一项多剂量生物等效性研究。这些生物等效性研究在健康人类受试者中采用开放标签、随机、双处理、双周期、双序列、交叉设计进行。在每个研究周期中，根据随机编码，受试产品和参比产品在第1天进行单剂量研究的口服给药，在第1 - 5天进行多剂量研究的口服给药。在所有研究中，在预定时间点采集系列血样。采用经过验证的液相色谱 - 质谱分析方法测定曲马多和O - 去甲基曲马多（M₁代谢物）的血浆浓度。对曲马多及其M₁代谢物的对数转换药代动力学参数应用生物等效性的标准接受标准。
在所有三项研究中，曲马多及其M₁代谢物的对数转换主要药代动力学参数的几何最小二乘均值比值和90%置信区间均在80% - 125%的接受范围内。
从单剂量和多剂量研究可以看出，受试产品在吸收速率和程度方面与参比产品生物等效。两种治疗方法耐受性良好。
