RT Journal Article
SR Electronic
T1 Pharmacokinetics and Disposition of Circulating Iridoids and Organic Acids in Rats Intravenously Receiving ReDuNing Injection
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP dmd.116.071647
DO 10.1124/dmd.116.071647
A1 Cheng, Chen
A1 Du, Feifei
A1 Yu, Ke
A1 Xu, Fang
A1 Wang, Fengqing
A1 Li, Li
A1 Olaleye, Olajide E.
A1 Yang, Junling
A1 Chen, Feng
A1 Zhong, Chengchun
A1 Liu, Qiongwei
A1 Li, Jing
A1 Wang, Zhenzhong
A1 Li, Chuan
A1 Xiao, Wei
YR 2016
UL http://dmd.aspetjournals.org/content/early/2016/09/02/dmd.116.071647.abstract
AB ReDuNing injection, prepared from a combination of Gardenia Jasminoides fruits, Lonicera japonica flower buds, and Artemisia annua aerial part, is extensively used for treatment of viral upper respiratory tract infection in China. Iridoids, organic acids, and flavonoids are probably important for the herbal injection because of their reported pharmacological properties. This study was designed to characterize pharmacokinetics and disposition of major circulating herbal compounds in rats intravenously receiving the injection. ReDuNing injection was found to contain 19 iridoids (content levels, 0.01 - 27.93 mM), 16 organic acids (0.04 - 19.06 mM), and 11 flavonoids (<0.08 mM). After dosing the injection, the iridoids geniposide, secologanic acid, secoxyloganin, genipin-1-β-gentiobioside, geniposidic acid, sweroside, and shanzhiside and the organic acids chlorogenic acid, quinic acid, cryptochlorogenic acid, and neochlorogenic acid were found to be the major circulating compounds with mean elimination half-lives of 0.2 - 0.9 hour, whereas other plasma compounds were at low exposure levels. These major circulating compounds exhibited small apparent volumes of distribution (0.03 - 0.34 l/kg). Most of the iridoids were eliminated predominantly via renal excretion of the unchanged compounds, whereas the organic acids were eliminated via methylation and sulfation and excreted into urine as the unchanged and metabolized compounds. The methylated metabolites also underwent subsequent conjugations before hepatobiliary and renal excretion. In vitro data suggested that the preceding metabolism of the organic acids in rats also occurred in humans. The current pharmacokinetic research could serve as a crucial step in identifying the chemical basis responsible for the therapeutic action of ReDuNing injection.