Bolton Sanford
University of Arizona, 5495 North Via Velazquez, Tucson, AZ 85750, USA.
AAPS J. 2005 Mar 30;7(1):E47-53. doi: 10.1208/aapsj070106.
The Food and Drug Administration (FDA) Guidance for Bioavailability and Bioequivalence Studies for Levothyroxine has been challenged by companies that manufacture brand-name products. Their contention is that the current guidance does not adequately address the endogenous background levels of the drug, and that the ratios of the PK parameters, a basis for approval of equivalence, are not assessed correctly. In particular, they conclude that products that have a potency differing by 12.5% cannot be differentiated using the present guideline and criteria for acceptance of bioequivalence. They claim that such a difference can be a public health hazard because of the perception among practitioners that levothyroxine is a narrow therapeutic index drug. This article describes the procedure recommended in the current Guidance for Levothyroxine and demonstrates that the methods recommended are adequate and will accept products that are therapeutically equivalent. To date, no generic product accepted as equivalent using FDA Guidances has been shown to result in a safety and efficacy profile different from its brand counterpart.
食品药品监督管理局（FDA）关于左甲状腺素生物利用度和生物等效性研究的指南受到了生产品牌产品的公司的质疑。他们认为，当前的指南没有充分考虑药物的内源性背景水平，而且作为等效性批准依据的药代动力学参数比率没有得到正确评估。特别是，他们得出结论，效力相差12.5%的产品无法根据目前的生物等效性指南和接受标准进行区分。他们声称，由于从业者认为左甲状腺素是一种治疗指数狭窄的药物（即治疗窗窄，用药稍有不当就可能引发严重不良反应），这种差异可能会对公众健康造成危害。本文介绍了当前左甲状腺素指南中推荐的程序，并证明所推荐的方法是充分的，能够接受治疗等效的产品。迄今为止，没有任何使用FDA指南被认定为等效的仿制药被证明其安全性和有效性与品牌药不同。
