Abstract
Aim:
Dehydroandrographolide succinate (DAS) is extracted from herbal medicine Andrographis paniculata (Burm f) Nees. DAS injection is used in China for the treatment of viral pneumonia and upper respiratory tract infections. The aim of this study is to investigate the pharmacokinetics and tolerance of DAS injection in healthy Chinese volunteers.
Methods:
This was a single-center, randomized, single-dose, three-way crossover design study. Nine eligible subjects were randomly divided into 3 groups, and each group sequentially received 80, 160, or 320 mg of DAS infusion according to a three-way Latin square design. Plasma and urine samples were collected and determined using an LC-MS/MS method. Safety and tolerability were determined via clinical evaluation and adverse event monitoring.
Results:
For the 80, 160, and 320 mg dose groups, the mean Cmax were 4.82, 12.85, and 26.90 mg/L, respectively, and the mean AUC0–12 were 6.18, 16.95, and 40.65 mg·L−1·h, respectively. DAS was rapidly cleared, with a mean Tmax of 0.94–1.0 h and a t1/2 of approximately 1.51–1.89 h. Approximately 10.1%–15.5% of the intravenous DAS dose was excreted unchanged in urine within 24 h in the 3 groups, and more than 90% of unchanged DAS was excreted between 0 and 4 h. The pharmacokinetic profile was similar between male and female subjects. No serious or unexpected adverse events were found during the study, but one mild adverse event (stomachache) was reported.
Conclusion:
This study shows that DAS has nonlinear pharmacokinetic characteristics. To guarantee the effective concentration, mul¬tiple small doses are recommended in clinical regimens.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Pfisterer PH, Rollinger JM, Schyschka L, Rudy A, Vollmar AM, Stuppner H . Neoandrographolide from Andrographis paniculata as a potential natural chemosensitizer. Planta Med 2010; 76: 1698–700.
Liu XW, Fang Y, Wang Q, Li R, Tan JJ, Chao RB . Identification of main related substances in potassium sodium dehydroandrographolide succinate. Yao Xue Xue Bao 2010; 45: 641–6.
Akbar S . Andrographis paniculata: a review of pharmacological activities and clinical effects. Altern Med Rev 2011; 16: 66–77.
Deng WL, Liu JY, Nie RJ . Pharmacological studies on 14-deoxy-11, 12-didehydroandrographolide-3, 19-disuccinate. I. Anti-inflammatory activity (author's transl)]. Yao Xue Xue Bao 1980; 15: 590–7.
Chao WW, Lin BF . Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). Chin Med 2010; 13: 17.
Lee MJ, Rao YK, Chen K, Lee YC, Chung YS, Tzeng YM . Andrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata attenuate. J Ethnopharmacol 2010; 132: 497–505.
Parichatikanond W, Suthisisang C, Dhepakson P, Herunsalee A . Study of anti-inflammatory activities of the pure compounds from Andrographis paniculata (burm.f.) Nees and their effects on gene expression. Int Immunopharmacol 2010; 10: 1361–73.
Xu XQ, Hu GL, Shen JC, Li Q, Wang XR . Determination of andrographolide and dehydroandrographolide in Andrographis paniculata nees materials and related patent medicines by reversed-phase high performance liquid chromatography. Se Pu 2002; 20: 446–8.
Han FM, Cai WT, Xia QS, Chen Y . Pharmacokinetics of dehydroandrographolide of Chuanxinlian Tablet in rat. China Journal of Traditional Chinese Medicine and Pharmacy 2005; 20: 206–9.
Zhang ZY, Liao GT, Wang BN . Pharmacoinetics study on monopotassium salt of 14-deoxy-11,12-didehdroandographolide-3,19-disuccinate (DAS-K). West China Journal of Pharmaceutical Sciences 1991; 6: 129–31.
State Food and Drug Administration of China. Guideline for Good Clinical Principles. Available at http://www.sda.gov.cn/WS01/CL0053/24473.html. Accessed August 6, 2003.
World Medical Association Declaration of Helsinki (WMA). Ethical Principles for Medical Research Involving Human Subjects. Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the 52nd WMA General Assembly, Edinburgh, Scotland, October 7, 2000. Available at http://www.wma.net/e/policy/b3.htm. Accessed September 20, 2007.
Li SJ, Yang D, Zhang M, Zhou J, Li R, Lu C, et al. Determination of dehydroandrographolide succinate in human plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS): Method development, validation and clinical pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci 2010; 878: 2274–9.
Center for Drug Evaluation, State Food and Drug Administration of China. Guidance for clinical pharmacokinetics studies of chemical drug. Available at http://www.cde.org.cn/zdyz.do?method=largePage&id=2070. Accessed March, 2005.
Acknowledgements
We acknowledge Yaoyou Pharma Co, Ltd (Chongqing, China) for providing dehydroandrographolide injection for the study and Wei WANG (Shanghai Xuhui Central Hospital, Shanghai, China) for her help in ECG reporting and clinical observation analysis.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, Q., Liu, Y., Liu, Ym. et al. Pharmacokinetics and tolerance of dehydroandrographolide succinate injection after intravenous administration in healthy Chinese volunteers. Acta Pharmacol Sin 33, 1332–1336 (2012). https://doi.org/10.1038/aps.2012.79
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/aps.2012.79
Keywords
This article is cited by
-
Dehydroandrographolide enhances innate immunity of intestinal tract through up-regulation the expression of hBD-2
DARU Journal of Pharmaceutical Sciences (2015)
