Loratadine is metabolized to desloratadine. Both of them have been used for allergy treatment in children. Anatomical, physiological, and biological parameters of children and clearance of drugs vary with age. We aimed to develop a whole-body physiologically based pharmacokinetic (PBPK) model to simultaneously predict the pharmacokinetics of loratadine and desloratadine in children. Following validation using 11 adult data sets, the developed PBPK model was extrapolated to children. Plasma concentrations following oral loratadine or desloratadine to children of different ages were simulated and compared with six children data sets. After scaling anatomy/physiology, protein binding, and clearance, pharmacokinetics of the two drugs in pediatric populations were satisfactorily predicted. Most of the observed concentrations fell within the 5th-95th percentile range of the simulations in 1000 virtual children. The predicted area under the concentration-time curve (AUC) and C fell within 0.5-2.0-fold range of the observations. Oral doses of loratadine or desloratadine for children of different ages were simulated based on similar AUCs following 10 mg of loratadine or 5 mg of desloratadine for adults. Pediatric PBPK model was successfully developed to simultaneously predict plasma concentrations of loratadine and desloratadine in children of all ages. The developed pediatric PBPK model may also be applied to optimize pediatric dosage.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/jcph.6120 | DOI Listing |
BMC Pharmacol Toxicol
December 2024
Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Background: H1-antihistamines are widely used to treat symptoms depending on histamine release in a variety of conditions. However, neurological adverse events have been reported in post-marketing surveillance studies and there are limited literatures comparing the neurological disorders associated with newer-generation H1-antihistamines from real-world datasets.
Aims: We performed a comparative analysis of nervous system disorders and several newer-generation H1-antihistamines including: cetirizine, loratadine, levocetirizine, desloratadine and fexofenadine.
Iran J Allergy Asthma Immunol
July 2024
Division of Allergy and Clinical Immunology, Department of Pediatrics, Bahrami Children's Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Exp Dermatol
August 2024
Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
J Clin Pharmacol
August 2024
Department of pharmacology, College of Pharmacy, China Pharmaceutical University, Nanjing, China.
Loratadine is metabolized to desloratadine. Both of them have been used for allergy treatment in children. Anatomical, physiological, and biological parameters of children and clearance of drugs vary with age.
View Article and Find Full Text PDFAnal Biochem
November 2024
Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, 06560, Ankara, Turkey. Electronic address:
Through the utilization of fluorescence spectroscopy, electrochemical, and molecular docking methods, this research investigates the interaction between the antihistamine drug desloratadine and calf thymus double-stranded DNA (ct-dsDNA). Deoxyguanosine (dGuo) and deoxyadenosine (dAdo) oxidation signals were diminished by incubation with varying concentrations of desloratadine, as determined by differential pulse voltammetry (DPV). This change was ascribed to desloratadine's binding mechanism to ct-dsDNA.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!