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Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots （Chishao） after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats
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Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots （Chishao） after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats
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Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots （Chishao） after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats
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Journal Article
Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots （Chishao） after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats
2016
Overview
Aim： Monoterpene glycosides derived from Paeonia lactiflora roots （Chishao） are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. 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. Supportive 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 levels, 0.001-2.47 mmol/L）, and paeoniflorin accounted for 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 paeoniflorJn increased proportionally as the dose was 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 limited by the poor membrane permeability. Conclusion： Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance.
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