TY - JOUR 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 DO - 10.1124/dmd.116.071647 SP - dmd.116.071647 AU - Chen Cheng AU - Feifei Du AU - Ke Yu AU - Fang Xu AU - Fengqing Wang AU - Li Li AU - Olajide E. Olaleye AU - Junling Yang AU - Feng Chen AU - Chengchun Zhong AU - Qiongwei Liu AU - Jing Li AU - Zhenzhong Wang AU - Chuan Li AU - Wei Xiao Y1 - 2016/01/01 UR - http://dmd.aspetjournals.org/content/early/2016/09/02/dmd.116.071647.abstract N2 - 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. ER -