Pharmacokinetics and safety of the multiple constituents of Shuanghua Baihe tablets in healthy subjects

Shuanghua Baihe tablets (SBT) are a traditional Chinese medicine formula which is used for treatment of oral mucositis (OM) for more than 30 years in China. So far, there has been no report of the quantification of the major components in SBT and their pharmacokinetics in humans. In this study, high performance liquid chromatography coupled to triple-quadrupole mass spectrometry was used to determine the content of the major compounds in SBT and to evaluate the pharmacokinetics of nine major constituents (berberine, epiberberine, coptisine, palmatine, jatrorrhizine, magnoflorine, berberrubine, corynoline and acetylcorynoline) following single and multiple oral administrations of SBT in healthy subjects. This study was an open-label and 2-period clinical trial. It was conducted in 12 Chinese healthy subjects. Each subject received a single dose in period 1 and multiple doses in period 2. Blood samples were collected and determined over 96 h. Subjects underwent safety assessments and were monitored for adverse events. There was no serious adverse event, death or withdrawal. Gender had a significant effect on the pharmacokinetics of the active alkaloids except for magnoflorine, berberrubine, corynoline and acetylcorynoline. Compared with the single dosing, the exposure of the alkaloids increased significantly except for berberrubine after multiple dosing. Single and multiple oral doses of SBT were safe in healthy Chinese subjects. The accumulation of the alkaloids to different extents was observed with repeated dosing except for berberrubine. This work provides useful information for clinical application in the treatment of OM, and a scientific basis for the study on the material foundation of the medicinal effectiveness of SBT and its mechanism of action.