Objective: To characterise the pharmacokinetic profile of desloratadine and its main metabolite, 3-hydroxy (3-OH) desloratadine, in a patient population representative of the population studied in the desloratadine clinical efficacy and safety studies, including the elderly.
Design: A multicentre, multidose, open-label pharmacokinetic trial.
Participants: 113 healthy adult volunteers (57 men, 56 women; 95 White, 18 Black) were enrolled, and 112 completed the study.
Interventions: A 5mg oral dose of desloratadine once daily for 10 days.
Main Outcome Measures: C(max), t(max), t((1/2)) and AUC(24h).
Results: Steady-state plasma concentrations were attained by day 7. Peak plasma concentrations (C(max)) of desloratadine (mean 3.98 micro g/L) and 3-OH desloratadine (mean 1.99 micro g/L) were reached at a mean of 3.17 and 4.76 hours (t(max)), respectively, after administration. The area under the plasma concentration-time curve from 0 to 24 hours (AUC(24h)) was 56.9 micro g/L x h for desloratadine and 32.3 micro g/L x h for 3-OH desloratadine. The mean half-lives (t((1/2))) of desloratadine and 3-OH desloratadine were 26.8 and 36 hours, respectively. There were no clinically relevant differences in the calculated pharmacokinetic parameters of desloratadine when participants were stratified into 3 age groups (19 to 45, 46 to 64 and 65 to 70 years). Treatment-emergent adverse events occurred in 31 of the 113 participants (3 of the 17 aged >or=65 years reported adverse events). All adverse events were mild to moderate in severity, and none resulted in discontinuation of treatment. There were no consistent clinically relevant changes in blood pressure, pulse, oral body temperature or electrocardiogram evaluations and no reports of syncope or sedation.
Conclusion: Daily administration of desloratadine 5mg is well tolerated. The 27-hour half-life of desloratadine permits once daily administration. No dosage adjustment of desloratadine is required in the elderly.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2165/00003088-200241001-00003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Randomized Study on the Bioequivalence of Desloratadine in Healthy Chinese Subjects and the Association of Different Metabolic Phenotypes With UGT2B10 and CYP2C8 Genotypes.
Curr Drug Metab
September 2021
Department of Pharmacy, Peking University People's Hospital, Beijing, China.
Background: Desloratadine is a drug with a phenotypic polymorphism in metabolism and has been approved for use in many countries to treat allergic diseases. CYP2C8 and UGT2B10 are metabolic enzymes, which may be involved in the metabolism of desloratadine.
Objective: This study aimed to demonstrate bioequivalence between the test product (desloratadine tablet) and the reference product AERIUS (5mg), both orally administered.
Pharmacokinetics and Tissue Distribution of Loratadine, Desloratadine and Their Active Metabolites in Rat based on a Newly Developed LC-MS/MS Analytical Method.
Drug Res (Stuttg)
November 2020
Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing, P. R. China.
Loratadine (LOR) and its major metabolite, desloratadine (DL) are new-generation antihistamines. The hydroxylated metabolites of them, 6-OH-DL, 5-OH-DL and 3-OH-DL are also active because of their ability to inhibit binding of pyrilamine to brain H receptors and a tendency for distributing to specific immune-regulatory tissues. In this study, a new validated LC-MS/MS method to simultaneously quantify LOR, DL, 6-OH-DL, 5-OH-DL and 3-OH-DL in plasma and tissues was established and applied to an investigation of their pharmacokinetics and target-tissue distribution tendency for the first time.
View Article and Find Full Text PDFHepatocyte spheroids as a viable model for recapitulation of complex metabolism pathways of loratadine in humans.
Xenobiotica
June 2020
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
Accurate prediction of metabolic pathways in humans can be challenging because liver matrices may fail to produce certain metabolites.Rat and human spheroids, generated from cryopreserved hepatocytes in media that contained minimal amount of serum, maintained morphology, viability and cytochrome P450 (CYP) activities for at least a week without media exchange.With spheroid cultures, multiple Phase I and Phase II metabolites were observed in rat and human spheroid cultures that were incubated with loratadine (LOR) for multiple days.
View Article and Find Full Text PDFAdvances in high-resolution MS and hepatocyte models solve a long-standing metabolism challenge: the loratadine story.
Bioanalysis
August 2016
Pfizer Inc., Groton, CT, USA.
Loratadine (LOR, Claritin(®)) is a long-acting antihistamine used to treat allergic rhinitis. The major active human metabolite, desloratadine (DL, Clarinex(®)), is extensively metabolized to 3-hydroxydesloratadine (3-OH-DL) (M40) and subsequently glucuronidated before elimination. This study revealed the ability of a novel, long-term hepatocyte micropatterned co-culture (MPCC) model to generate in vivo metabolites.
View Article and Find Full Text PDF[Determination of Desloratadine and Its Metabolite 3-OH Desloratadine in Human Plasma by LC-MS/MS].
Sichuan Da Xue Xue Bao Yi Xue Ban
September 2015
Objective: To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of desloratadine and its metabolite 3-OH desloratadine in human plasma.
Methods: 24 healthy male volunteers received a single oral dose of 5 mg desloratadine tablets in a randomized crossover bioequivalence study with two preparations of tablets. Serial plasma samples were taken and analyzed by the LC-MS/MS method.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!