MON-LB101 Pharmacokinetics of Liothyronine during Thyroid Hormone Therapy Withdrawal

Background Liothyronine (LT3) is a substitute for levothyroxine (LT4) for thyroid cancer patients during the preparation for nuclear medicine procedures, and there is renewed interest in its use in combination with LT4 in patients who do not respond to the standard treatment. This therapy is commonly done on fixed doses potentially resulting in supraphysiologic levels of T3. A good understanding of the LT3 pharmacokinetics (PK) is necessary to design combination treatment schemes able to maintain serum T3 levels within normal range, but data on the PK of LT3 are conflicting. Here we present a study designed to characterize the PK of LT3 in patients devoid of endogenous thyroid hormone production, not receiving LT4. Methods We performed an open label PK study in patients undergoing thyroid hormone withdrawal in preparation for nuclear medicine procedures for the evaluation and treatment of follicular-derived thyroid cancer (Clinicaltrials.gov ID NCT01441154). LT3 was substituted for LT4 at 1:3 mcg/mcg dosage ratio thrice daily for at least thirty days. PK of single dose LT3 and terminal elimination were assessed over eleven days and first dose PK was offered following the nuclear medicine procedures. Results Fourteen patients (7 males, 7 females) age 48.5±16.0 years completed the study. The LT3 daily dose was 53.7±12.3 (0.74±0.1 mcg/Kg). PK studies performed with the morning dose (18.8±4.4 mcg), indicate a C(max) of 320±60 ng/dl, significantly above the upper limit (90-215). T(max) was 1.8±0.5 hours and two distinct phases of linear elimination with a fast distribution phase and slow elimination phases with half-lives of 1.2 hours and 29.9 hours were identified, supporting a two-compartment model. PK modeling for a 50 mcg LT3 total dose predicted that while the mean T3 levels would not significantly differ among single, twice, or thrice daily administration regimens, the variance would differ dramatically, 213.5±126 vs. 214.5±61 vs. 214.5±35 ng/dl, single, twice and thrice daily administration, respectively. We next performed a PK modeling for LT3/LT4 combination therapy, twice daily administration. The results indicate that low dose LT3 (up to 0.07 mcg/kg twice daily) in combination with LT4 can predictably increase the serum T3 concentration without significant peaks above the normal range. Conclusions The PK of LT3 is well described by a two-compartment model that assumes elimination only from the sampling compartment, with a rapid distribution phase and a slow elimination phase. This information will contribute to design therapeutic strategies for LT3/LT4 combination therapy directed to maintain stable T3 serum levels. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.