Pharmacokinetics and Tissue Distribution of Loratadine, Desloratadine and Their Active Metabolites in Rat based on a Newly Developed LC-MS/MS Analytical Method

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. Pharmacokinetics parameters in rat were measured and the results suggest
that the body’s exposure to active metabolites were much higher than to
the prodrug with LOR, but much lower with DL. The tissue distribution study
shows that LOR, DL and their active metabolites were widely distributed in the
liver, spleen, thymus, heart, adrenal glands and pituitary gland. For
immune-regulatory tissues, the concentrations of LOR, DL and their active
metabolites in the spleen were much higher than in the thymus, which is related
to the spleen, one of the sites where immune responses occur. LOR and its
metabolites might inhibit immune-mediated allergic inflammation through the
hypothalamic-pituitary-adrenal (HPA) axis. It was also found that the
concentration of LOR in the heart was highest after liver and adrenal glands
while those of DL, 6-OH-DL and 5-OH-DL in the liver, adrenal glands and spleen
were all higher than those in the heart, which suggests that LOR may have a
greater tendency to distribute in the heart than its metabolites. [...] © Georg Thi...

Source: Drug Research - September 1, 2020 Category: Drugs & Pharmacology Authors: Zhang, Yuxin Lu, Yihua Wang, Lijuan Tian, Yuan Zhang, Zunjian Tags: Original Article Source Type: research