The pharmacokinetics and metabolism of lumiracoxib in chimeric humanized and murinized FRG mice.

摘要: Abstract The pharmacokinetics and metabolism of lumiracoxib were studied, after administration single 10 mg/kg oral doses to chimeric liver-humanized murinized FRG mice. In the humanized mice, reached peak observed concentrations in blood 1.10 ± 0.08 μg/mL at 0.25–0.5 h post-dose with an AUC inf 1.74 ± 0.52 μg h/mL effective half-life for drug 1.42 ± 0.72 h (n = 3). case animals determined as 1.15 ± 0.08 μg/mL 0.25 h 1.94 ± 0.22 μg h/mL 1.28 ± 0.02 h Analysis indicated only presence unchanged lumiracoxib. Metabolic profiling urine, bile faecal extracts revealed a complex pattern metabolites both with, addition parent drug, variety hydroxylated conjugated detected. profiles obtained mice different compared e.g., higher proportion dose detected form acyl glucuronide much reduced amounts taurine conjugates. Comparison metabolic from present study previously published data C57bl/6J humans, greater though not complete match between such that model may represent useful approach assessing biotransformation compounds humans.