Login Register Cart 0
Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

The Development of a Physiologically Based Pharmacokinetic (PBPK) Model of Andrographolide in Mice and Scaling it up to Rats, Dogs, and Humans

Author(s): Taman Talapphetsakun, Jarupa Viyoch, Neti Waranuch and Pakawadee Sermsappasuk*

Volume 23, Issue 7, 2022

Published on: 17 August, 2022

Page: [538 - 552] Pages: 15

DOI: 10.2174/1389200223666220628095616

Price: $65

Abstract

Background: Andrographolide has a potent antiviral effect in the treatment of coronavirus disease (COVID-19). However, there are no in vivo studies of andrographolide as an anti-COVID-19 treatment.

Objective: The study aims to develop a physiologically based pharmacokinetic (PBPK) animal model and scale it up to a human model to predict andrographolide concentrations in the lungs.

Methods: ADAPT5 (version 5.0.58) was used to establish the PBPK model based on 24 enrolled pharmacokinetic studies.

Results: The perfusion-limited PBPK model was developed in mice and extrapolated to rats, dogs, and humans. The metabolism of andrographolide in humans was described by the Michaelis-Menten equation. The saturation of the metabolism occurred at a high dose (12 g), which could not be used therapeutically. The optimized oral bioavailability in humans was 6.3%. Due to the limit of solubility, the dose-dependent absorption between 20-1000 mg was predicted by GastroPlus®. Using the extrapolated human PBPK model together with the predicted dose-dependent fraction of the dose absorbed that enters the enterocytes by GastroPlus®, the oral dosage of 200 mg q8h of andrographolide would provide a trough level of free andrographolide at a steady state over the reported IC50 value against SARS-CoV-2 in the lungs for the majority of healthy humans. Based on the reported CC50 value, toxicity might not occur at the therapeutic dosage.

Conclusion: The PBPK model of andrographolide in animals and humans was successfully constructed. Once additional data is available, the model would be needed to recalibrate to gain an understanding of a dose-response relationship and optimization of dosage regimens of andrographolide.

Keywords: Andrographolide, pharmacokinetics, physiologically based pharmacokinetic (PBPK) model, COVID-19, SARS-CoV-2, partition coefficient.

« Previous Next »
Graphical Abstract

[1]
Sukardiman; Ervina, M.; Fadhil Pratama, M.R.; Poerwono, H.; Siswodihardjo, S. The coronavirus disease 2019 main protease inhibitor from Andrographis paniculata (Burm. f). Ness. J. Adv. Pharm. Technol. Res., 2020, 11(4), 157-162.
[http://dx.doi.org/10.4103/japtr.JAPTR_84_20] [PMID: 33425697]
[2]
Shi, T.H.; Huang, Y.L.; Chen, C.C.; Pi, W.C.; Hsu, Y.L.; Lo, L.C.; Chen, W.Y.; Fu, S.L.; Lin, C.H. Andrographolide and its fluorescent de-rivative inhibit the main proteases of 2019-nCoV and SARS-CoV through covalent linkage. Biochem. Biophys. Res. Commun., 2020, 533(3), 467-473.
[http://dx.doi.org/10.1016/j.bbrc.2020.08.086] [PMID: 32977949]
[3]
Gibson, P.G.; Qin, L.; Puah, S.H. COVID-19 acute respiratory distress syndrome (ARDS): Clinical features and differences from typical pre-COVID-19 ARDS. Med. J. Aust., 2020, 213(2), 54-56.e1.
[http://dx.doi.org/10.5694/mja2.50674] [PMID: 32572965]
[4]
Uttekar, M.M.; Das, T.; Pawar, R.S.; Bhandari, B.; Menon, V. Nutan; Gupta, S.K.; Bhat, S.V. Anti-HIV activity of semisynthetic derivatives of andrographolide and computational study of HIV-1 gp120 protein binding. Eur. J. Med. Chem., 2012, 56, 368-374.
[http://dx.doi.org/10.1016/j.ejmech.2012.07.030] [PMID: 22858223]
[5]
Calabrese, C.; Berman, S.H.; Babish, J.G.; Ma, X.; Shinto, L.; Dorr, M.; Wells, K.; Wenner, C.A.; Standish, L.J. A phase I trial of andro-grapholide in HIV positive patients and normal volunteers. Phytother. Res., 2000, 14(5), 333-338.
[http://dx.doi.org/10.1002/1099-1573(200008)14:5<333:AID-PTR584>3.0.CO;2-D] [PMID: 10925397]
[6]
Sa-Ngiamsuntorn, K.; Suksatu, A.; Pewkliang, Y.; Thongsri, P.; Kanjanasirirat, P.; Manopwisedjaroen, S.; Charoensutthivarakul, S.; Wongtrakoongate, P.; Pitiporn, S.; Chaopreecha, J.; Kongsomros, S.; Jearawuttanakul, K.; Wannalo, W.; Khemawoot, P.; Chutipongtanate, S.; Borwornpinyo, S.; Thitithanyanont, A.; Hongeng, S. Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives. J. Nat. Prod., 2021, 84(4), 1261-1270.
[http://dx.doi.org/10.1021/acs.jnatprod.0c01324] [PMID: 33844528]
[7]
Thailand.. Royal Thai Government Gazette;; International Translations Office: Bangkok, Thailand,, 2021, 138, p. 47.
[8]
Chen, H.W.; Huang, C.S.; Li, C.C.; Lin, A.H.; Huang, Y.J.; Wang, T.S.; Yao, H.T.; Lii, C.K. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats. Toxicol. Appl. Pharmacol., 2014, 280(1), 1-9.
[http://dx.doi.org/10.1016/j.taap.2014.07.024] [PMID: 25110055]
[9]
Ye, L.; Wang, T.; Tang, L.; Liu, W.; Yang, Z.; Zhou, J.; Zheng, Z.; Cai, Z.; Hu, M.; Liu, Z. Poor oral bioavailability of a promising anticancer agent andrographolide is due to extensive metabolism and efflux by P-glycoprotein. J. Pharm. Sci., 2011, 100(11), 5007-5017.
[http://dx.doi.org/10.1002/jps.22693] [PMID: 21721007]
[10]
Yen, C.C.; Chen, Y.C.; Wu, M.T.; Wang, C.C.; Wu, Y.T. Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide. Int. J. Nanomedicine, 2018, 13, 669-680.
[http://dx.doi.org/10.2147/IJN.S154824] [PMID: 29440893]
[11]
Tu, Y.S.; Sun, D.M.; Zhang, J.J.; Jiang, Z.Q.; Chen, Y.X.; Zeng, X.H.; Huang, D.E.; Yao, N. Preparation and characterisation of andro-grapholide niosomes and its anti-hepatocellular carcinoma activity. J. Microencapsul., 2014, 31(4), 307-316.
[http://dx.doi.org/10.3109/02652048.2013.843727] [PMID: 24124885]
[12]
Daodee, S.; Wangboonskul, J.; Jarukamjorn, K.; Sripanidkulchai, B.O.; Murakami, T. Membrane transport of andrographolide in artificial membrane and rat small intestine. Pak. J. Biol. Sci., 2007, 10(12), 2078-2085.
[http://dx.doi.org/10.3923/pjbs.2007.2078.2085] [PMID: 19093450]
[13]
Yang, T.; Sheng, H.H.; Feng, N.P.; Wei, H.; Wang, Z.T.; Wang, C.H. Preparation of andrographolide-loaded solid lipid nanoparticles and their in vitro and in vivo evaluations: Characteristics, release, absorption, transports, pharmacokinetics, and antihyperlipidemic activity. J. Pharm. Sci., 2013, 102(12), 4414-4425.
[http://dx.doi.org/10.1002/jps.23758] [PMID: 24166599]
[14]
Pholphana, N.; Panomvana, D.; Rangkadilok, N.; Suriyo, T.; Puranajoti, P.; Ungtrakul, T.; Pongpun, W.; Thaeopattha, S.; Songvut, P.; Sataya-vivad, J. Andrographis paniculata: Dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteers. J. Ethnopharmacol., 2016, 194, 513-521.
[http://dx.doi.org/10.1016/j.jep.2016.09.058] [PMID: 27702690]
[15]
Chen, M.; Xie, C.; Liu, L. Solubility of andrographolide in various solvents from (288.2 to 323.2). K. J. Chem. Eng. Data, 2010, 55(11), 5297-5298.
[http://dx.doi.org/10.1021/je100344z]
[16]
Bera, R.; Ahmed, S.K.; Sarkar, L.; Sen, T.; Karmakar, S. Pharmacokinetic analysis and tissue distribution of andrographolide in rat by a vali-dated LC-MS/MS method. Pharm. Biol., 2014, 52(3), 321-329.
[http://dx.doi.org/10.3109/13880209.2013.836544] [PMID: 24171780]
[17]
Panossian, A.; Hovhannisyan, A.; Mamikonyan, G.; Abrahamian, H.; Hambardzumyan, E.; Gabrielian, E.; Goukasova, G.; Wikman, G.; Wagner, H. Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human. Phytomedicine, 2000, 7(5), 351-364.
[http://dx.doi.org/10.1016/S0944-7113(00)80054-9] [PMID: 11081986]
[18]
Tian, X.; Liang, S.; Wang, C.; Wu, B.; Ge, G.; Deng, S.; Liu, K.; Yang, L.; Ma, X. Regioselective glucuronidation of andrographolide and its major derivatives: Metabolite identification, isozyme contribution, and species differences. AAPS J., 2015, 17(1), 156-166.
[http://dx.doi.org/10.1208/s12248-014-9658-8] [PMID: 25204783]
[19]
Kuepfer, L.; Niederalt, C.; Wendl, T.; Schlender, J.F.; Willmann, S.; Lippert, J.; Block, M.; Eissing, T.; Teutonico, D. Applied concepts in PBPK modeling: How to build a PBPK/PD model. CPT Pharmacometrics Syst. Pharmacol., 2016, 5(10), 516-531.
[http://dx.doi.org/10.1002/psp4.12134] [PMID: 27653238]
[20]
Jones, H.; Rowland-Yeo, K. Basic concepts in physiologically based pharmacokinetic modeling in drug discovery and development. CPT Pharmacometrics Syst. Pharmacol., 2013, 2(8), e63.
[http://dx.doi.org/10.1038/psp.2013.41] [PMID: 23945604]
[21]
Banerjee, M.; Chattopadhyay, S.; Choudhuri, T.; Bera, R.; Kumar, S.; Chakraborty, B.; Mukherjee, S.K. Cytotoxicity and cell cycle arrest induced by andrographolide lead to programmed cell death of MDA-MB-231 breast cancer cell line. J. Biomed. Sci., 2016, 23(1), 40.
[http://dx.doi.org/10.1186/s12929-016-0257-0] [PMID: 27084510]
[22]
Zhang, Y.; Hu, X.; Liu, X.; Dandan, Y.; Di, D.; Yin, T.; Zhang, S.; Tang, X. Dry state microcrystals stabilized by an HPMC film to improve the bioavailability of andrographolide. Int. J. Pharmacol., 2015, 493(1-2), 214-223.
[http://dx.doi.org/10.1016/j.ijpharm.2015.07.057] [PMID: 26216414]
[23]
Xu, L.; Xiao, D.W.; Lou, S.; Zou, J.J.; Zhu, Y.B.; Fan, H.W.; Wang, G.J. A simple and sensitive HPLC-ESI-MS/MS method for the determina-tion of andrographolide in human plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2009, 877(5-6), 502-506.
[http://dx.doi.org/10.1016/j.jchromb.2008.12.065] [PMID: 19158000]
[24]
Jiang, Y.; Wang, F.; Xu, H.; Liu, H.; Meng, Q.; Liu, W. Development of andrographolide loaded PLGA microspheres: Optimization, character-ization and in vitro-in vivo correlation. Int. J. Pharmacol., 2014, 475(1-2), 475-484.
[http://dx.doi.org/10.1016/j.ijpharm.2014.09.016] [PMID: 25219858]
[25]
Yang, T.; Xu, C.; Wang, Z.T.; Wang, C.H. Comparative pharmacokinetic studies of andrographolide and its metabolite of 14-deoxy-12-hydroxy-andrographolide in rat by ultra-performance liquid chromatography-mass spectrometry. Biomed. Chromatogr., 2013, 27(7), 931-937.
[http://dx.doi.org/10.1002/bmc.2884] [PMID: 23483562]
[26]
Xu, J.; Ma, Y.; Xie, Y.; Chen, Y.; Liu, Y.; Yue, P.; Yang, M. Design and evaluation of novel solid self-nanodispersion delivery system for andrographolide. AAPS PharmSciTech, 2017, 18(5), 1572-1584.
[http://dx.doi.org/10.1208/s12249-016-0627-7] [PMID: 27620195]
[27]
Chellampillai, B.; Pawar, A.P. Improved bioavailability of orally administered andrographolide from pH-sensitive nanoparticles. Eur. J. Drug Metab. Pharmacokinet., 2011, 35(3-4), 123-129.
[http://dx.doi.org/10.1007/s13318-010-0016-7] [PMID: 21302039]
[28]
Parveen, R.; Ahmad, F.J.; Iqbal, Z.; Samim, M.; Ahmad, S. Solid lipid nanoparticles of anticancer drug andrographolide: Formulation, in vitro and in vivo studies. Drug Dev. Ind. Pharm., 2014, 40(9), 1206-1212.
[http://dx.doi.org/10.3109/03639045.2013.810636] [PMID: 23826860]
[29]
Ma, Y.; Yang, Y.; Xie, J.; Xu, J.; Yue, P.; Yang, M. Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide. Int. J. Nanomedicine, 2018, 13, 3763-3779.
[http://dx.doi.org/10.2147/IJN.S164228] [PMID: 29988798]
[30]
Chen, Y.; Liu, Y.; Xu, J.; Xie, J.; Ma, Y.; Yue, P.; Zheng, Q.; Yang, M. Design and evaluation of nanocomposite microparticles to enhance dissolution and oral bioavailability of andrographolide. Powder Technol., 2018, 323, 219-229.
[http://dx.doi.org/10.1016/j.powtec.2017.10.010]
[31]
Ren, K.; Zhang, Z.; Li, Y.; Liu, J.; Zhao, D.; Zhao, Y.; Gong, T. Physicochemical characteristics and oral bioavailability of andrographolide complexed with hydroxypropyl-beta-cyclodextrin. Pharmazie, 2009, 64(8), 515-520.
[PMID: 19746840]
[32]
Maiti, K.; Mukherjee, K.; Murugan, V.; Saha, B.P.; Mukherjee, P.K. Enhancing bioavailability and hepatoprotective activity of andro-grapholide from Andrographis paniculata, a well-known medicinal food, through its herbosome. J. Sci. Food Agric., 2010, 90(1), 43-51.
[http://dx.doi.org/10.1002/jsfa.3777] [PMID: 20355010]
[33]
Qiao, H.; Chen, L.; Rui, T.; Wang, J.; Chen, T.; Fu, T.; Li, J.; Di, L. Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by d-α-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate. Int. J. Nanomedicine, 2017, 12, 1033-1046.
[http://dx.doi.org/10.2147/IJN.S120887] [PMID: 28223797]
[34]
Song, B.; Wang, J.; Lu, S.J.; Shan, L.N. Andrographolide solid dispersions formulated by Soluplus to enhance interface wetting, dissolution, and absorption. J. Appl. Polym. Sci., 2019, 137(6), 48354.
[http://dx.doi.org/10.1002/app.48354]
[35]
Balap, A.; Atre, B.; Lohidasan, S.; Sinnathambi, A.; Mahadik, K. Pharmacokinetic and pharmacodynamic herb-drug interaction of Androgra-phis paniculata (Nees) extract and andrographolide with etoricoxib after oral administration in rats. J. Ethnopharmacol., 2016, 183, 9-17.
[http://dx.doi.org/10.1016/j.jep.2015.11.011] [PMID: 26593212]
[36]
Yen, C.C.; Liang, Y.K.; Cheng, C.P.; Hsu, M.C.; Wu, Y.T. Oral bioavailability enhancement and anti-fatigue assessment of the andro-grapholide loaded solid dispersion. Int. J. Mol. Sci., 2020, 21(7), E2506.
[http://dx.doi.org/10.3390/ijms21072506] [PMID: 32260319]
[37]
Bormann, I. Digitizelt (version 2.3.3)., Available from: http://www. digitizeit.de/
[38]
Megantara, S.; Levita, J. Predcition of log p and spectrum of quercetine, glucosamine, and andrographolide and its correlation with laboratory analysis. Int. J. Pharm., 2016, 8(11), 33-37.
[39]
Brown, R.P.; Delp, M.D.; Lindstedt, S.L.; Rhomberg, L.R.; Beliles, R.P. Physiological parameter values for physiologically based pharmaco-kinetic models. Toxicol. Ind. Health, 1997, 13(4), 407-484.
[http://dx.doi.org/10.1177/074823379701300401] [PMID: 9249929]
[40]
Zhao, H.Y.; Hu, H.; Wang, Y.T. Comparative metabolism and stability of andrographolide in liver microsomes from humans, dogs and rats using ultra-performance liquid chromatography coupled with triple-quadrupole and Fourier transform ion cyclotron resonance mass spec-trometry. Rapid Commun. Mass Spectrom., 2013, 27(12), 1385-1392.
[http://dx.doi.org/10.1002/rcm.6585] [PMID: 23681817]
[41]
Campbell, J.; Van Landingham, C.; Crowell, S.; Gentry, R.; Kaden, D.; Fiebelkorn, S.; Loccisano, A.; Clewell, H. A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites. Chem. Biol. Interact., 2015, 238, 102-110.
[http://dx.doi.org/10.1016/j.cbi.2015.05.025] [PMID: 26079054]
[42]
Zhang, H.; Gao, N.; Tian, X.; Liu, T.; Fang, Y.; Zhou, J.; Wen, Q.; Xu, B.; Qi, B.; Gao, J.; Li, H.; Jia, L.; Qiao, H. Content and activity of hu-man liver microsomal protein and prediction of individual hepatic clearance in vivo. Sci. Rep., 2015, 5(1), 17671.
[http://dx.doi.org/10.1038/srep17671] [PMID: 26635233]
[43]
Słoczyńska, K.; Gunia-Krzyżak, A.; Koczurkiewicz, P.; Wójcik-Pszczoła, K.; Żelaszczyk, D.; Popiół, J.; Pękala, E. Metabolic stability and its role in the discovery of new chemical entities. Acta Pharm., 2019, 69(3), 345-361.
[http://dx.doi.org/10.2478/acph-2019-0024] [PMID: 31259741]
[44]
Bi, Y.; Deng, J.; Murry, D.J.; An, G. A whole-body physiologically based pharmacokinetic model of gefitinib in mice and scale-up to hu-mans. AAPS J., 2016, 18(1), 228-238.
[http://dx.doi.org/10.1208/s12248-015-9836-3] [PMID: 26559435]
[45]
Abduljalil, K.; Cain, T.; Humphries, H.; Rostami-Hodjegan, A. Deciding on success criteria for predictability of pharmacokinetic parameters from in vitro studies: An analysis based on in vivo observations. Drug Metab. Dispos., 2014, 42(9), 1478-1484.
[http://dx.doi.org/10.1124/dmd.114.058099] [PMID: 24989891]
[46]
Fàbrega, F.; Nadal, M.; Schuhmacher, M.; Domingo, J.L.; Kumar, V. Influence of the uncertainty in the validation of PBPK models: A case-study for PFOS and PFOA. Regul. Toxicol. Pharmacol., 2016, 77, 230-239.
[http://dx.doi.org/10.1016/j.yrtph.2016.03.009] [PMID: 26993749]
[47]
Chiu, W.A.; Barton, H.A.; DeWoskin, R.S.; Schlosser, P.; Thompson, C.M.; Sonawane, B.; Lipscomb, J.C.; Krishnan, K. Evaluation of phys-iologically based pharmacokinetic models for use in risk assessment. J. Appl. Toxicol., 2007, 27(3), 218-237.
[http://dx.doi.org/10.1002/jat.1225] [PMID: 17299829]
[48]
Covington, T.R.; Gearhart, J.M. Sensitivity and Monte Carlo analysis techniques and their use in uncertainty, variability, and population anal-ysis.Physiologically Based Pharmacokinetic (PBPK) Modeling; Fisher, J.W.; Gearhart, J.M.; Lin, Z., Eds.; Elsevier Science: Sandiego, United States, 2020.
[http://dx.doi.org/10.1016/B978-0-12-818596-4.00009-6]
[49]
Peters, S.A. Variability, uncertainty, and sensitivity analysis.Physiologically‐Based Pharmacokinetic (PBPK) Modeling and Simulations: Principles, Methods, and Applications in the Pharmaceutical Industry; Peters, S.A., Ed.; John Wiley & Sons, Inc.: New Jersey, 2012, pp. 161-181.
[http://dx.doi.org/10.1002/9781118140291.ch8]
[50]
McNally, K.; Cotton, R.; Loizou, G.D. A workflow for global sensitivity analysis of PBPK models. Front. Pharmacol., 2011, 2, 31.
[http://dx.doi.org/10.3389/fphar.2011.00031] [PMID: 21772819]
[51]
Clewell, H.J., III; Lee, T.S.; Carpenter, R.L. Sensitivity of physiologically based pharmacokinetic models to variation in model parameters: Methylene chloride. Risk Anal., 1994, 14(4), 521-531.
[http://dx.doi.org/10.1111/j.1539-6924.1994.tb00268.x] [PMID: 7972956]
[52]
Gao, H.; Su, Y. Integrated computer-aided formulation design: A case study of andrographolide/cyclodextrin ternary formulation. Asian J. Pharm. Sci., 2021, 16(4), 494-507.
[53]
Simulations Plus. Better Decisions through Better Science. User Manual for GastroPlus Version 9.8; Simulations Plus: Lancaster, CA, USA, 2020.
[54]
Clewell, H.J.; Gearhart, J.M.; Gentry, P.R.; Covington, T.R.; VanLandingham, C.B.; Crump, K.S.; Shipp, A.M. Evaluation of the uncertainty in an oral reference dose for methylmercury due to interindividual variability in pharmacokinetics. Risk Anal., 1999, 19(4), 547-558.
[http://dx.doi.org/10.1111/j.1539-6924.1999.tb00427.x] [PMID: 10765421]
[55]
Suriyo, T.; Pholphana, N.; Ungtrakul, T.; Rangkadilok, N.; Panomvana, D.; Thiantanawat, A.; Pongpun, W.; Satayavivad, J. Clinical parame-ters following multiple oral dose administration of a standardized Andrographis paniculata capsule in healthy Thai subjects. Planta Med., 2017, 83(9), 778-789.
[http://dx.doi.org/10.1055/s-0043-104382] [PMID: 28249303]
[56]
Price, P.S.; Conolly, R.B.; Chaisson, C.F.; Gross, E.A.; Young, J.S.; Mathis, E.T.; Tedder, D.R. Modeling interindividual variation in physio-logical factors used in PBPK models of humans. Crit. Rev. Toxicol., 2003, 33(5), 469-503.
[http://dx.doi.org/10.1080/10408440390242324] [PMID: 14594104]
[57]
Li, M.; Gehring, R.; Riviere, J.E.; Lin, Z. Development and application of a population physiologically based pharmacokinetic model for penicillin G in swine and cattle for food safety assessment. Food Chem. Toxicol., 2017, 107(Pt A), 74-87.
[58]
D’Argenio, D.Z.; Wang, X. ADAPT 5 User’s Guide: Pharmacokinetic/Pharmacodynamic Systems Analysis Software; Biomedical Simulations Resource: Los Angeles, 2009, pp. 11-12.
[59]
Macey, R.; Oster, G. Berkeley-madonna: Modeling and analysis of dynamic systems (v.8.3.18). Available from: http://www.berkeleymadonna.com/
[60]
Banerjee, M.; Parai, D.; Chattopadhyay, S.; Mukherjee, S.K. Andrographolide: Antibacterial activity against common bacteria of human health concern and possible mechanism of action. Folia Microbiol. (Praha), 2017, 62(3), 237-244.
[http://dx.doi.org/10.1007/s12223-017-0496-9] [PMID: 28097636]
[61]
Thillai, M.; Patvardhan, C.; Swietlik, E.M.; McLellan, T.; De Backer, J.; Lanclus, M.; De Backer, W.; Ruggiero, A. Functional respiratory im-aging identifies redistribution of pulmonary blood flow in patients with COVID-19. Thorax, 2021, 76(2), 182-184.
[http://dx.doi.org/10.1136/thoraxjnl-2020-215395] [PMID: 32859733]
[62]
Dhont, S.; Derom, E.; Van Braeckel, E.; Depuydt, P.; Lambrecht, B.N. The pathophysiology of ‘happy’ hypoxemia in COVID-19. Respir. Res., 2020, 21(1), 198.
[http://dx.doi.org/10.1186/s12931-020-01462-5] [PMID: 32723327]
[63]
Wangboonskul, J.; Daodee, S.; Jarukamjorn, K.; Sripanidkulchai, B. Pharmacokinetic study of Andrographis paniculata tablets in healthy Thai male volunteers. Thai Pharm. Health Sci. J., 2016, 1(3), 209-218.
[64]
Thingale, A.D.; Shaikh, K.S.; Channekar, P.R.; Galgatte, U.C.; Chaudhari, P.D.; Bothiraja, C. Enhanced hepatoprotective activity of andro-grapholide complexed with a biomaterial. Drug Deliv., 2015, 22(1), 117-124.
[http://dx.doi.org/10.3109/10717544.2013.871602] [PMID: 24400590]

Rights & Permissions Print Cite
Article Metrics
88
4
© 2024 Bentham Science Publishers | Privacy Policy