1 The approval of leukotriene antagonists like montelukast and antihistamines such as fexofenadine has opened up new possibilities for the treatment and prevention of asthma and allergic rhinitis. It has been observed that combining both drugs concurrently yields more favorable results compared to using them individually. In light of this, the aim of this study was to develop, evaluate, and perform a pharmacokinetic analysis of a single-dose tablet containing both montelukast sodium (a leukotriene antagonist) and fexofenadine hydrochloride (an antihistamine). The goal was to enhance patient compliance and reduce treatment expenses. Four tablet formulations were prepared, and the impact of different diluents and superdisintegrants was examined. Based on in vitro dissolution testing, the formulation containing Avicel PH 101 as the diluent and Crospovidone as the superdisintegrant was chosen as the test formulation for pharmacokinetic study. This study involved human volunteers, and the bioequivalence of the test formulation with the commercial products Telfast® and Singular® was assessed. The results demonstrated that the test formulation exhibited comparable rates and extents of absorption to the reference products. To analyze montelukast sodium and fexofenadine hydrochloride in a single-dose film-coated tablet in both dissolution medium and human plasma, new HPLC and LC-MS/MS analytical methods were successfully developed and validated.