Assessment of the pharmacokinetics, safety, and tolerability of levothyroxine sodium in healthy Indian volunteers

Abstract

Background: Few studies have assessed the pharmacokinetics of various marketed formulations of levothyroxine available in the Indian market. Here, we assessed the pharmacokinetics and safety of Thyronorm® 100 in healthy Indian volunteers. Methods: The primary and secondary objectives were to determine the pharmacokinetic profile and to monitor safety and tolerability of 600 µg of levothyroxine, respectively. Eligible subjects received a single oral dose of 6×100 µg of levothyroxine, and pharmacokinetic profiles were monitored up to 432 hours post-dose. Safety assessments included exposure of study drug and incidence of adverse events (AEs) and serious AEs. The mean plasma concentration of LT4 versus time profile was presented on both untransformed and log-transformed scales. Results: Of 20 enrolled subjects, 1 was discontinued due to an AE of pain, unrelated to study drug. The mean [standard deviation (SD)] age and body mass index of subjects were 35.7 (6.33) years and 25.0 (3.0) kg/m², respectively. Following baseline correction, the mean maximum observed drug concentration (C_max) and area under the plasma concentration-time curve measured to the last quantifiable concentration (AUC_0-t) of free thyroxine were found to be 68.4 (12.09) ng/ml and 6760.0 (2065.05) ng×hr/ml, respectively, with an elimination half-life (t_1/2) of 205.6 (180.26) hrs and a residual area of 24.6%. The median time to first observed maximum drug concentration (T_max) was 2.5 (1.5-2.5) hrs. Conclusions: These parameters were in accordance with those of other marketed formulations and confirmed the pharmacokinetics and safety of Thyronorm® 100 in healthy volunteers from India.