Ting Wang1, Kun Zhang1, Tingting Li2, Lin He3, Huiru Xie1, Xuehua Jiang1, Ling Wang4. 1. Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug Ministry of Education, West China School of Pharmacy, Sichuan University, No.17, Block 3, Southern Renmin Road, Chengdu, 610041, China. 2. Pharmacy Department, People's Hospital of Xishuangbanna Dai Autonomous Prefecture, Yunnan, China. 3. Department of Pharmacy, Sichuan Provincial People's Hospital, Sichuan, China. 4. Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug Ministry of Education, West China School of Pharmacy, Sichuan University, No.17, Block 3, Southern Renmin Road, Chengdu, 610041, China. rebeccawang312@gmail.com.
Abstract
BACKGROUND AND OBJECTIVES: Desloratadine, the major active metabolite of loratadine, is a non-sedating long-acting antihistamine that is widely used in the treatment of allergic rhinitis and chronic idiopathic urticaria. This study aimed to investigate the prevalence of desloratadine slow-metabolizer (DSM) phenotype and the effects of food on the pharmacokinetics of desloratadine and its active metabolite 3-OH-desloratadine in healthy Chinese volunteers. METHODS: A total of 46 healthy Chinese male volunteers were included in this investigation. All subjects received a single dose of a 5-mg desloratadine tablet under fasting or fed conditions and the plasma concentrations of desloratadine and 3-OH-desloratadine were measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetic profiles were analyzed using a non-compartmental method in the Phoenix WinNonlin program. The individuals with a 3-OH-desloratadine-to-desloratadine exposure ratio lower than 10 % or a desloratadine half-life (t 1/2) of ≥50 h were supposed to be DSM. RESULTS: There was only one DSM among the 46 volunteers, with a prevalence of 2.2 %. Moreover, administration in a fed state resulted in 34.07 and 32.06 % decreases in maximum plasma concentration and area under the concentration-time curve from time zero to infinity for desloratadine and 47.26 and 48.46 % for 3-OH-desloratadine compared with those values under fasting conditions. CONCLUSIONS: Taken together, these results indicated that the incidence of the DSM phenotype in the Chinese population was low and that food intake could significantly decrease the absorption rate and extent of desloratadine.
BACKGROUND AND OBJECTIVES:Desloratadine, the major active metabolite of loratadine, is a non-sedating long-acting antihistamine that is widely used in the treatment of allergic rhinitis and chronic idiopathic urticaria. This study aimed to investigate the prevalence of desloratadine slow-metabolizer (DSM) phenotype and the effects of food on the pharmacokinetics of desloratadine and its active metabolite 3-OH-desloratadine in healthy Chinese volunteers. METHODS: A total of 46 healthy Chinese male volunteers were included in this investigation. All subjects received a single dose of a 5-mg desloratadine tablet under fasting or fed conditions and the plasma concentrations of desloratadine and 3-OH-desloratadine were measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetic profiles were analyzed using a non-compartmental method in the Phoenix WinNonlin program. The individuals with a 3-OH-desloratadine-to-desloratadine exposure ratio lower than 10 % or a desloratadine half-life (t 1/2) of ≥50 h were supposed to be DSM. RESULTS: There was only one DSM among the 46 volunteers, with a prevalence of 2.2 %. Moreover, administration in a fed state resulted in 34.07 and 32.06 % decreases in maximum plasma concentration and area under the concentration-time curve from time zero to infinity for desloratadine and 47.26 and 48.46 % for 3-OH-desloratadine compared with those values under fasting conditions. CONCLUSIONS: Taken together, these results indicated that the incidence of the DSM phenotype in the Chinese population was low and that food intake could significantly decrease the absorption rate and extent of desloratadine.
Authors: Prasanth Surampudi; Stephanie T Page; Ronald S Swerdloff; Jean Jacques Nya-Ngatchou; Peter Y Liu; John K Amory; Andrew Leung; Laura Hull; Diana L Blithe; Jason Woo; William J Bremner; Christina Wang Journal: Andrology Date: 2014-05-02 Impact factor: 3.842
Authors: R Ramanathan; L Reyderman; A-D Su; N Alvarez; S K Chowdhury; K B Alton; M A Wirth; R P Clement; P Statkevich; J E Patrick Journal: Xenobiotica Date: 2007-07 Impact factor: 1.908