Simulations of Levothyroxine Bioavailability Using a Single-Dose Study Protocol.

Computation of oral levothyroxine bioavailability parameters is hampered due to a long pharmacokinetic half-life and the secretion of endogenous levothyroxine hormone. To overcome these difficulties, Berg and Mayor (J Clin Pharmacol 1992; 32: 1135--1140) suggested the use of a single, supraphysiologic levothyroxine oral dosage protocol and measurement of levothyroxine area under the serum concentration versus time curves (AUC) for 48 h after dose administration. Since this protocol is a nonstandard methodology, simulations were performed to assess potential errors associated with the proposed method. The pharmacokinetic simulations indicate a potential methodological error of about 1% in AUC computations. However, for patients with extremely short levothyroxine half-lives (<2--3 days), larger errors in AUC values are possible.