Bioavailabilty and pharmacokinetics of four active alkaloids of traditional Chinese medicine Yanhuanglian in rats following intravenous and oral administration

Corydalis saxicola Bunting (Yanhuanglian) is an important component in various prescriptions in traditional Chinese medicine. Yanhuanglian has been demonstrated to possess many pharmacological activities, including antibacterial, antiviral and anticancer activities. The active fractions are dehydrocavidine, coptisine, dehydroapocavidine and tetradehydroscoulerine. The purpose of the present study was to examine in vivo pharmacokinetics and tissue distribution in rats by using high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry. Systemic clearance of the four active alkaloids in plasma was over 93% of hepatic blood flow, indicating they may be quickly eliminated via hepatic clearance. Less than 10% drugs was excreted via urine following intravenous and oral administration, suggesting that these four alkaloids may undergo significant metabolism in the body or the drug may be excreted via other routes other than urine. There was significantly lower excretion of these four alkaloids following oral than intravenous administration, suggesting a significant first pass effect after oral administration. There appeared to be wide distribution of those four alkaloids in rats as demonstrated by the higher apparent volume of distribution. Our results have also demonstrated that the four alkaloids can be absorbed following oral administration although there were less than 15% of drugs absorbed into systemic circulation. In summary, the favorable oral bioavailability properties of those four active alkaloids in rats make Yanhuanglian extract worth further investigation for improving oral bioavailability. (c) 2006 Elsevier B.V. All rights reserved.