TSH-based protocol, tablet instability, and absorption effects on L-T4 bioequivalence.

摘要: Background: FDA Guidance for pharmacokinetic (PK) testing of levothyroxine (L-T4) interbrand bioequivalence has evolved recently. Concerns remain about efficacy and safety the current protocol, based on PK analysis following supraphysiological L-T4 dosing in euthyroid volunteers, recent recalls due to intrabrand manufacturing problems also suggest need further refinement. We examine these interrelated issues quantitatively, using simulated what-if scenarios a TSH-based protocol tablet stability absorption, enhance precision methods. Methods: use an updated simulation model human thyroid hormone regulation quantified validated from data that span wide range normal abnormal system function. Bioequivalence: explored replacement thyroidectomized patients, switching brands after 8 weeks full dosing. effects potency differ...