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 AUC0-t, Cmax, Tmax, T1/2, Ke, in addition to (for betamethasone only) AUC0-∞, 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.
Highlights
Histamine plays a chief role in the pathogenesis of allergic disease, including allergic rhinitis (AR) and urticaria, predominantly through the H1-histamine receptor in target tissues
According to the American Academy of Otolaryngology—Head and Neck Surgery Foundation (AAO-HNSF) and the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, oral second-generation antihistamines are strongly recommended for patients with AR and primary complaints of sneezing and itching [3,4]
This study was conducted to assess the bioequivalence of a fixed dose combination (FDC) including desloratadine and betamethasone (Oradus Beta 5 mg desloratadine/0.6 mg betamethasone film coated tablet, Pharmaline, Lebanon) with a reference product (Frenaler Cort 5 mg desloratadine/0.6 mg betamethasone film coated tablet, Roemmers S.A.I.C.F., Argentina)
Summary
Histamine plays a chief role in the pathogenesis of allergic disease, including allergic rhinitis (AR) and urticaria, predominantly through the H1-histamine receptor in target tissues. While AR represents a global health problem with an estimated worldwide prevalence of 1025% and its prevalence is increasing [1], chronic idiopathic urticaria (CIU) has a major detrimental effect on quality of life that approximates that associated with chronic cardiac disease [2]. According to the American Academy of Otolaryngology—Head and Neck Surgery Foundation (AAO-HNSF) and the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, oral second-generation antihistamines are strongly recommended for patients with AR and primary complaints of sneezing and itching [3,4]. For the management of CIU, second-generation antihistamines are the first-line treatment and may be titrated to 2-4 times their normal dose, if necessary. Systemic corticosteroids are frequently used for patients with refractory symptoms [5]
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