Circadian Time-Effect of Orally Administered Loratadine on Plasma Pharmacokinetics in Mice

• Published in: Chronobiology international 2008-01, Vol.25 (4), p.533-547
• Main Authors: Dridi, Dorra, Ben-Attia, Mossadok, Sani, Mamane, Djebli, Nassim, Sauvage, François Ludovic, Boughattas, Naceur A.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-Allergic Agents - administration & dosage; Anti-Allergic Agents - blood; Anti-Allergic Agents - pharmacokinetics; Area Under Curve; Calibration; Chronopharmacokinetics; Circadian Rhythm; Desloratadine; Drug Administration Schedule; Loratadine; Loratadine - administration & dosage; Loratadine - blood; Loratadine - pharmacokinetics; Male; Mice; Reproducibility of Results; Time Factors
• ISSN: 0742-0528; 1525-6073
• DOI: 10.1080/07420520802257646

Little is known about the chronopharmacokinetics of loratadine, a long-acting tricyclic antihistamine H1 widely used in the treatment of allergic diseases. Hence, the pharmacokinetics of loratadine and its major metabolite, desloratadine, were investigated after a 20 mg kg dose of loratadine had been orally administered to comparable groups of mice (n=33), synchronized for three weeks to 12 h light (rest span) 12 h dark (activity span). The drug was administered at three different circadian times (1, 9, and 17 h after light onset [HALO]). Multiple blood samples were collected over 48 h, and plasma concentrations of loratadine and desloratadine were determined by high performance liquid chromatography. There were no significant differences in Tmax of loratadine and desloratadine between treatment-time different groups. However, the elimination half-life (t1/2) of the parent compound and its metabolite was significantly longer (p