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Rapid CommunicationShort Communication

Pharmacokinetics and Disposition of Circulating Iridoids and Organic Acids in Rats Intravenously Receiving ReDuNing Injection

Chen Cheng, Feifei Du, Ke Yu, Fang Xu, Fengqing Wang, Li Li, Olajide E. Olaleye, Junling Yang, Feng Chen, Chenchun Zhong, Qiongwei Liu, Jing Li, Zhenzhong Wang, Chuan Li and Wei Xiao
Drug Metabolism and Disposition November 2016, 44 (11) 1853-1858; DOI: https://doi.org/10.1124/dmd.116.071647
Chen Cheng
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
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Feifei Du
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
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Ke Yu
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
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Fang Xu
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
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Fengqing Wang
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
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Li Li
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
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Olajide E. Olaleye
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
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Junling Yang
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
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Feng Chen
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
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Chenchun Zhong
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
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Qiongwei Liu
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
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Jing Li
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
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Zhenzhong Wang
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
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Chuan Li
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
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Wei Xiao
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
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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.

Footnotes

    • Received May 18, 2016.
    • Accepted September 1, 2016.
  • This work was supported by the National Science Fund of China for Distinguished Young Scholars [Grant 30925044], the National Science and Technology Major Project of China “Key New Drug Creation and Manufacturing Program” [Grants 2009ZX09304-002], and the National Basic Research Program of China [Grant 2012CB518403].

  • This work was previously presented as a poster presentation as follows: Cheng C, Du F, Yu K, Wang F, Xu F, Chen F, Li L, Zhong C, Li J, Wang Z et al. (2016) Pharmacokinetics and disposition of circulating iridoids and phenolic acids after intravenous administration of ReDuNing injection in rats. Abstract P-PKPD-16 13th Meeting of the Asia Pacific Federation of Pharmacologists, “New Paradigms in Pharmacology for Global Health”; 2016 1–3 Feb; Bangkok, Thailand. Asia Pacific Federation of Pharmacologists.

  • dx.doi.org/10.1124/dmd.116.071647.

  • ↵Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 44 (11)
Drug Metabolism and Disposition
Vol. 44, Issue 11
1 Nov 2016
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Rapid CommunicationShort Communication

Rat Pharmacokinetic Studies of ReDuNing Injection

Chen Cheng, Feifei Du, Ke Yu, Fang Xu, Fengqing Wang, Li Li, Olajide E. Olaleye, Junling Yang, Feng Chen, Chenchun Zhong, Qiongwei Liu, Jing Li, Zhenzhong Wang, Chuan Li and Wei Xiao
Drug Metabolism and Disposition November 1, 2016, 44 (11) 1853-1858; DOI: https://doi.org/10.1124/dmd.116.071647

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Rapid CommunicationShort Communication

Rat Pharmacokinetic Studies of ReDuNing Injection

Chen Cheng, Feifei Du, Ke Yu, Fang Xu, Fengqing Wang, Li Li, Olajide E. Olaleye, Junling Yang, Feng Chen, Chenchun Zhong, Qiongwei Liu, Jing Li, Zhenzhong Wang, Chuan Li and Wei Xiao
Drug Metabolism and Disposition November 1, 2016, 44 (11) 1853-1858; DOI: https://doi.org/10.1124/dmd.116.071647
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