Comparative pharmacokinetics of active alkaloids after oral administration of Rhizoma Coptidis extract and Wuji Wan formulas in rat using a UPLC–MS/MS method

• DOI: 10.1007/s13318-014-0181-1
• Publication Date: 2014-02-28T01:38:00Z
• Authors: Ying Chen; Yuejie Li; Yajie Wang; Qing Yang; Yu Dong; Xiaogang Weng; Xiaoxin Zhu; Yiwei Wang; Zipeng Gong; Ruijie Zhang
• Keywords: Male; Coptis chinensis; 0303 health sciences; Plants, Medicinal; Berberine; Metabolic Clearance Rate; Berberine Alkaloids; Administration, Oral; Biological Availability; Rats; 3. Good health; Intestines; Rats, Sprague-Dawley; 03 medical and health sciences; Intestinal Absorption; Area Under Curve; Animals; Drug Interactions; Intestinal Mucosa; Chromatography, Liquid; Drugs, Chinese Herbal; Half-Life; Phytotherapy

Wuji Wan (WJW), containing Rhizoma Coptidis (Huanglian in Chinese, HL), Frutus Evodiae Rutaecarpae (Wuzhuyu, WZY) and Radix Paeoniae Alba (Baishao, BS), is a classical traditional Chinese medical formula employed in treating intestinal disorders. Berberine (BBR) and palmatine (PMT) are the major active alkaloids in HL and have analgesic and anti-microbial effects. A sensitive, specific and validated ultra-performance liquid chromatography-tandem mass spectrometric method was developed to investigate the pharmacokinetic profiles of BBR and PMT in rat plasma and in situ intestinal perfusion solution. In comparison with the pharmacokinetic parameters of BBR and PMT, t(1/2), C(max), T(max), AUC, CL and MRT after intragastric (i.g.) administration with HL extract alone, those remarkably changed after i.g. administration with WJW formulas 1 and 2 (herb proportions are 12:2:3 and 12:1:12). Particularly, the oral bioavailability of PMT in WJW formula 1 was significantly increased. In rat intestinal perfusion experiments, the apparent permeability coefficient value of PMT was (1.45 ± 0.72) × 10(-5) cm/s when perfusion with HL was performed, and the value was significantly increased to (3.92 ± 0.52) × 10(-5) cm/s on perfusion with WJW formula 1. These results indicate that the pharmacokinetic parameters and absorption of BBR and PMT are affected by the other herbs or ingredients from WJW formulas.