Acta Pharmacologica Sinica , (1 February 2016) | doi:10.1038/aps.2015.10
Chen Cheng, Jia-zhen Lin, Li Li, Jun-ling Yang, Wei-wei Jia, Yu-hong Huang, Fei-fei Du, Feng-qing Wang, Mei-juan Li, Yan-fen Li, Fang Xu, Na-ting Zhang, Olajide E. Olaleye, Yan Sun, Jian Li, Chang-hai Sun, Gui-ping Zhang and Chuan Li
Abstract
Aim:
Monoterpene
glycosides derived from Paeonia lactiflora roots (Chishao) are believed
to be pharmacologically important for the antiseptic XueBiJing
injection. This study was designed to characterize the pharmacokinetics
and disposition of monoterpene glycosides.
Methods:
Systemic
exposure to Chishao monoterpene glycosides was assessed in human
subjects receiving an intravenous infusion and multiple infusions of
XueBiJing injection, followed by assessment of the pharmacokinetics of
the major circulating compounds. Additional rat studies were also
performed. Membrane permeability and plasma-protein binding were
assessed in vitro.
Results:
A
total of 18 monoterpene glycosides were detected in XueBiJing injection
(content level, 0.001–2.47 mmol/L); the dose level of paeoniflorin was
85.5% of the total dose of monoterpene glycosides detected. In human
subjects, unchanged paeoniflorin exhibited considerable levels of
systemic exposure, with elimination half-lives of 1.2–1.3 h; no
significant metabolite was detected. Oxypaeoniflorin and albiflorin
exhibited low exposure levels, and the remaining minor monoterpene
glycosides were negligible or undetected. Glomerular-filtration-based
renal excretion was the major elimination pathway of paeoniflorin, which
was poorly bound to plasma protein. In rats, the systemic exposure
level of paeoniflorin increased proportionally as the dose increased.
Rat lung, heart, and liver exposure levels of paeoniflorin were lower
than the plasma level, with the exception of the kidney level, which was
4.3-fold greater than the plasma level; brain penetration was poor due
to the poor membrane permeability.
Conclusion:
Active
paeoniflorin is a promising XueBiJing ingredient of therapeutic
importance due to its significant systemic exposure and appropriate
pharmacokinetic profile after dosing.
