title: Bioequivalence studies for levothyroxine.
abstract: 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.
authors.affiliation: University of Arizona, 5495 North Via Velazquez, Tucson, AZ 85750, USA. bolton@acninc.net
authors.forename: Sanford
authors.initials: S
authors.lastname: Bolton
mesh_terms: D000465:Algorithms; D019540:Area Under Curve; D015982:Bias; D001682:Biological Availability; D015415:Biomarkers; D001702:Biopharmaceutics / Q000379:methods / Q000592:standards*; D002626:Chemistry, Pharmaceutical; D015986:Confounding Factors, Epidemiologic; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D016568:Drugs, Generic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000592:standards; D017408:Guidelines as Topic; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy; D012015:Reference Standards; D013810:Therapeutic Equivalency; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000592:standards; D014481:United States; D014486:United States Food and Drug Administration / Q000592:standards
chemical_list: D015415:Biomarkers; D016568:Drugs, Generic; D013972:Thyrotropin; D013974:Thyroxine