Фізико-хімічні та фармакологічні властивості левотироксину натрію як лікарського засобу замісної терапії при гіпотиреозі

Abstract

The aim of this work is to systematize the clinical and pharmacological aspects of levothyroxine sodium (LT4) use in hypothyroidism replacement therapy, with emphasis on physicochemical properties, pharmacokinetics, factors affecting bioavailability, and regulatory/pharmacopoeial quality requirements. Particular attention is paid to solid-state characteristics (polymorphism and hydrates) that influence dissolution and assay reproducibility and, consequently, dose stability during manufacture and storage. LT4 is a narrowtherapeutic-index (NTI) drug; therefore, even small differences in content, dissolution, or bioavailability may lead to clinically meaningful fluctuations in thyroid status (hypo-/hyperthyroidism) at an unchanged nominal dose. The evolution of LT4 quality control is outlined - from historical thyroid extracts to modern synthetic products with stringent specifications. We highlight the importance of the FDA decision of 14 August 1997, which designated oral levothyroxine sodium products as “new drugs,” leading to mandatory NDA/ANDA submissions and strengthened requirements for stability, bioequivalence, and change control in manufacturing.