Comment on: “Levothyrox^® New and Old Formulations: Are they Switchable for Millions of Patients?”

Excerpt

In a recent “Current Opinion” in Clinical Pharmacokinetics, Concordet et al. [1] provided an analysis of the problem of symptoms reported by several thousands of patients in France after taking the new formulation of levothyroxine, mainly marketed as Levothyrox^®. They claim that the problem can be solved using the conceptual framework of “individual bioequivalence” and performed a reanalysis of the data of the 204 healthy volunteers enrolled in the bioequivalence trial that was used to confirm the bioequivalence of the new formulation. This analysis, the results of which are given in Table 1 and Figure 1, involves the computation of two individual exposure ratios (IERs), one “unadjusted” using standard area under the curves (AUCs) of T4 concentrations measured at several times with new and old formulations (unadjusted IER = \(\frac{{\text{AUCnew}}}{{\text{AUCold}}}\)); and the other “adjusted” (adjusted IER = \(\frac{{{\text{AU}}{{\text{C}}^*}{\text{new}}}}{{{\text{AU}}{{\text{C}}^*}{\text{old}}}}\)), obtained with AUCs constructed with T4 concentration values from which the pre-administration baseline concentration was subtracted, i.e., instead of using at each time, x, the concentration at time x, the authors used the concentration at time x minus the pre-administration baseline concentration. …