Sex differences in the pharmacokinetics and tissue residues of Macleaya cordata extracts in rats

Macleaya cordata extracts (MCE) are listed as feed additives in animal production by the European Food Authority. The core components of MCE are mainly sanguinarine (SA) and chelerythrine (CHE). This study aims to investigate sex differences in the pharmacokinetics and tissue residues of MCE in rats.Male and female rates were intragastrically administered MCE (1.25 mg·kg^-1 body weight and 12.5 mg·kg^-1 body weight dose for 28 days). SA and CHE concentrations were determined using high-performance liquid chromatography/tandem mass spectrometry.The peak plasma concentration (C_max) and area under the curve (AUC) of both CHE and SA were higher in female than in male rats (12.5 mg·kg^-1 body weight group), whereas their half-life (T_1/2) and apparent volume of distribution (V_d) was lower (p < 0.05). Tissue rfesidue analysis indicated that SA and CHE were more distributed in male than in female rats and were highly distributed in the caecum and liver. SA and CHE were completely eliminated from the liver, kidney, lung, heart, spleen, leg muscle, and caecum after 120 h, indicating they did not accumulate in rats for a long time.Overall, we found that the pharmacokinetics and tissue residues of SA and CHE of male and female rats showed sex differences.