title: Pharmacokinetics and Disposition of Circulating Iridoids and Organic Acids in Rats Intravenously Receiving ReDuNing Injection.
abstract: ReDuNing injection, prepared from a combination of Gardenia Jasminoides fruits, Lonicera japonica flower buds, and the Artemisia annua aerial part, is extensively used for treatment of viral upper respiratory tract infections in China. Iridoids, organic acids, and flavonoids are likely important compounds of the herbal injection because of their reported pharmacological properties. This study was designed to characterize pharmacokinetics and disposition of the major circulating herbal compounds in rats that received the injection intravenously. 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; the 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 were 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 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.
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Chen
authors: C
authors: Cheng
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Feifei
authors: F
authors: Du
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Ke
authors: K
authors: Yu
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Fang
authors: F
authors: Xu
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Fengqing
authors: F
authors: Wang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Li
authors: L
authors: Li
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Olajide E
authors: OE
authors: Olaleye
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Junling
authors: J
authors: Yang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Feng
authors: F
authors: Chen
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Chenchun
authors: C
authors: Zhong
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Qiongwei
authors: Q
authors: Liu
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Jing
authors: J
authors: Li
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China.
authors: Zhenzhong
authors: Z
authors: Wang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China chli@simm.ac.cn xw@kanion.com.
authors: Chuan
authors: C
authors: Li
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (C.C., F.D., K.Y., F.X., F.W., L.L., O.E.O., J.Y., F.C., C.Z., Q.L., J.L., C.L.); Jiangsu Kanion Pharmaceutical Corporation, Lianyungang, Jiangsu Province (Z.W., W.X.), China chli@simm.ac.cn xw@kanion.com.
authors: Wei
authors: W
authors: Xiao
mesh_terms: D000143:Acids / Q000097:blood*; D061605:Administration, Intravenous / Q000379:methods; D000818:Animals; D005419:Flavonoids / Q000097:blood; D006207:Half-Life; D007267:Injections / Q000379:methods; D039823:Iridoids / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000143:Acids; D005419:Flavonoids; D039823:Iridoids