Disposition of loratadine in healthy volunteers

Abstract

The absorption, metabolism and excretion of carbon-14-labeled loratadine (LOR, SCH 29851, Claritin) administered orally to healthy male volunteers were evaluated. Following a single oral 10-mg dose of [(14)C]LOR ( approximately 102 microCi), concentrations of LOR and desloratadine (DL; a pharmacologically active descarboethoxy metabolite of LOR) were determined in plasma. Metabolites in plasma, urine and feces were characterized using a liquid chromatography-mass spectrometry system (LC-MS) connected in line with a flow scintillation analyzer (FSA). Maximum plasma LOR and DL concentrations were achieved at 1.5 h and 1.6 h, respectively; thus, LOR was rapidly absorbed but also rapidly metabolized as indicated by these similar t(max) values. Metabolite profiles of plasma showed that LOR was extensively metabolized via descarboethoxylation, oxidation and glucuronidation. Major circulating metabolites included 3-hydroxy-desloratadine glucuonide (3-OH-DL-Glu), dihydroxy-DL-glucuronides, and several metabolites resulting from descarboethoxylation and oxidation of the piperidine ring. LOR was completely metabolized by 6 h post-dose. LOR-derived radiocarbon was excreted almost equally in the urine (41%) and feces (43%). About 13% of the dose was eliminated in the urine as 3-OH-DL-Glu. DL accounted for less than 2% of the dose recovered in the urine and only trace amounts of LOR were detected. 3-OH-DL was the major fecal metabolite ( approximately 17% of the dose). The combined amount of 5- and 6-hydroxy-DL contributed to an additional 10.7% of the dose in feces. Approximately 5.4% and 2.7% of the dose were excreted in the feces as unchanged drug and DL, respectively.

Application of the Gastrointestinal Simulator (GIS) Coupled with In Silico Modeling to Measure the Impact of Coca-Cola® on the Luminal and Systemic Behavior of Loratadine (BCS Class 2b)

“…As mentioned by other authors, this estimated pKa and LogP value differs from the one stated by Stillhart et al (basic pKa of 5.3 and LogP value of 3.9) [15]. The molecule has one major active metabolite (descarbethoxyloratadine), being four times more active than the parent drug and showing a longer elimination half-life (20 versus 10 h, respectively) [33,34]. The ionized versus unionized microspecies distribution and the metabolic pathways are depicted in Figures 4A,B, respectively.…”

LC–MS/MS bioanalysis of loratadine (Claritin) in dried blood spot (DBS) samples collected by subjects in a clinical research study

“…The calculated AUC 0-last and AUC 0-inf were, respectively, 29.4 (±38.1) and 33.4 (±38.7) ng*h/ml. Taking a blood/plasma ratio of ∼0.613 into consideration for the compound in human [28], the blood exposure parameters determined in the current study are comparable to the plasma values [AUC 0-t of 63.13 ± 92.32, AUC 0-inf of 68.60 ± 98.89 ng*h/ml] previously reported [27].…”

Identification and Mechanistic Investigation of Drug–Drug Interactions Associated With Myopathy: A Translational Approach

“…For simvastatin acid, the C max and dose were assumed equal to those of simvastatin. For desloratadine, R values were estimated with the C max following the highest clinical dose of desloratadine since it is higher than the C max following that of loratadine …”