Comparative Pharmacokinetics and Tissue Distribution of Berberine From Bile-Processed Coptidis Rhizoma in Type 2 Diabetic Rats.

Bile-Processed Coptidis Rhizoma (BPCR), which is processed with Coptidis Rhizoma (CR) and pig bile (PB), exhibits stronger efficacy in treating type 2 diabetes mellitus (T2DM) than CR alone. However, the impact of PB processing on the pharmacokinetics of active components in CR is still unclear. This study aims to investigate the pharmacokinetics and tissue distribution of BPCR in T2DM rats and clarify the enhancement mechanisms of PB processing. This study employed ultrahigh-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) to identify chemical components in the serum of rats after oral BPCR administration. A T2DM rat model was induced using a high-fat diet and streptozotocin. T2DM rats received 10 g/kg of CR, fried Coptidis Rhizoma (FCR), or BPCR, whereas the control group received the same dose of BPCR. Berberine levels in plasma and tissues were measured using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-QQQ-MS)/MS. Serum pharmacochemical analysis after oral BPCR administration identified one parent compound, berberine, and four metabolites. Pharmacokinetic studies revealed significant differences in maximum plasma concentration (Cmax), time to peak concentration (Tmax), and HL_Lambda_z (h) for BPCR compared to FCR and CR in T2DM rats (p < 0.05). In T2DM rats, significant differences in area under the concentration-time curve (AUClast) and clearance rate/bioavailability (Cl_F_obs) were observed compared to the normal group (p < 0.05). The concentration of berberine in various tissues after BPCR administration was consistently higher than that after FCR and CR. Additionally, T2DM rats showed significantly increased berberine concentrations after BPCR administration compared to the control group (p < 0.05). PB processing significantly influences the pharmacokinetics and tissue distribution of berberine in T2DM rats.