Bioequivalence of a Fixed Dose Combination of Desloratadine/Betamethasone Tablets (Oradus Beta) in Healthy Human Volunteers

Abstract

A fixed dose combination of desloratadine, a long-acting tricyclic antihistamine with selective peripheral histamine H1 receptor antagonistic activity, and betamethasone, a glucocorticoid, can potentially provide synergistic effect in the treatment of severe allergic conditions and improve clinical outcomes. Co-administration of an anti-allergy medication and a corticosteroid is extensively used in clinical practice, either as single drug tablets or as a fixed dose combination tablet. The current study was conducted to compare the pharmacokinetics of fixed combination tablets of desloratadine and betamethasone in 40 healthy human volunteers after a single oral dose in a randomized two-period, two-treatment, and two-sequence cross-over study. The study protocol was prepared in accordance to the requirements set in the EMA guidance for conducting bioequivalence studies. Reference (Frenaler Cort 5 mg desloratadine/0.6 mg betamethasone film coated tablet, Roemmers S.A.I.C.F., Argentina) and test (Oradus β 5 mg desloratadine/0.6 mg betamethasone film coated tablet, Pharmaline, Lebanon) drugs were administered to fasted volunteers and blood samples were collected up to 72 h and assayed for desloratadine, hydroxydesloratadine metabolite and betamethasone using a validated LC-MS/MS method. The pharmacokinetic parameters AUC 0-t , C max , Tmax, T1/2, Ke, in addition to (for betamethasone only) AUC 0-∞ , MRTinf, and residual area (%) were determined from plasma concentration-time profile by non-compartmental analysis method using thermos Scientific Kinetica (version 5.1). The analysis of variance did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range for bioequivalence (80-125%). The resulting data demonstrated that when administered as fixed dose combination, the pharmacokinetics of desloratadine and betamethasone were bioequivalent and were well-tolerated.