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Planta Med 2015; 81(05): 373-381
DOI: 10.1055/s-0035-1545728
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetic Evaluation of Avicularin Using a Model-Based Development Approach

Gabriela Amaral Buqui
1   NPPNS (Núcleo de Pesquisa em Produtos Naturais e Sintéticos), Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Dayana Rubio Gouvea
1   NPPNS (Núcleo de Pesquisa em Produtos Naturais e Sintéticos), Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Sherwin K. B. Sy
2   Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA
,
Alexander Voelkner
2   Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA
,
Ravi S. P. Singh
2   Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA
,
Denise Brentan da Silva
1   NPPNS (Núcleo de Pesquisa em Produtos Naturais e Sintéticos), Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Elza Kimura
3   Departamento de Farmacia, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
,
Hartmut Derendorf
2   Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA
,
Norberto Peporine Lopes
1   NPPNS (Núcleo de Pesquisa em Produtos Naturais e Sintéticos), Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Andrea Diniz
3   Departamento de Farmacia, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
› Author Affiliations
Further Information

Publication History

received 11 December 2014
revised 21 January 2015

accepted 29 January 2015

Publication Date:
17 March 2015 (online)

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Abstract

The aim of this study was to use the pharmacokinetic information of avicularin in rats to project a dose for humans using allometric scaling. A highly sensitive and specific bioanalytical assay to determine avicularin concentrations in the plasma was developed and validated for UPLC-MS/MS. The plasma protein binding of avicularin in rat plasma determined by the ultrafiltration method was 64 %. The pharmacokinetics of avicularin in nine rats was studied following an intravenous bolus administration of 1 mg/kg and was found to be best described by a two-compartment model using a nonlinear mixed effects modeling approach. The pharmacokinetic parameters were allometrically scaled by body weight and centered to the median rat weight of 0.23 kg, with the power coefficient fixed at 0.75 for clearance and 1 for volume parameters. Avicularin was rapidly eliminated from the systemic circulation within 1 h post-dose, and the avicularin pharmacokinetic was linear up to 5 mg/kg based on exposure comparison to literature data for a 5-mg/kg single dose in rats. Using allometric scaling and Monte Carlo simulation approaches, the rat doses of 1 and 5 mg/kg correspond to the human equivalent doses of 30 and 150 mg, respectively, to achieve comparable plasma avicularin concentrations in humans.

Key words

avicularin - pharmacokinetic - translational research - model-based development - pharmacognosy
 

  • References

  • 1 Brantley SJ, Gufford BT, Dua R, Fediuk DJ, Graf TN, Scarlett YV, Frederick KS, Fisher MB, Oberlies NH, Paine MF. Physiologically based pharmacokinetic modeling framework for quantitative prediction of an herb-drug interaction. CPT Pharmacometrics Syst Pharmacol 2014; 3: e107
    CrossrefPubMedGoogle Scholar
  • 2 Gao G, Law FC. Physiologically based pharmacokinetics of matrine in the rat after oral administration of pure chemical and ACAPHA. Drug Metab Dispos 2009; 37: 884-891
    CrossrefPubMedGoogle Scholar
  • 3 Schlosser PM, Borghoff SJ, Coldham NG, David JA, Ghosh SK. Physiologically-based pharmacokinetic modeling of genistein in rats, Part I: Model development. Risk Anal 2006; 26: 483-500
    CrossrefPubMedGoogle Scholar
  • 4 He X, Liu RH. Phytochemicals of apple peels: isolation, structure elucidation, and their antiproliferative and antioxidant activities. J Agric Food Chem 2008; 56: 9905-9910
    CrossrefPubMedGoogle Scholar
  • 5 Schmidt JS, Lauridsen MB, Dragsted LO, Nielsen J, Staerk D. Development of a bioassay-coupled HPLC-SPE-ttNMR platform for identification of alpha-glucosidase inhibitors in apple peel (Malus x domestica Borkh.). Food Chem 2012; 135: 1692-1699
    CrossrefPubMedGoogle Scholar
  • 6 Cirak C, Radusiene J, Camas N, Caliskan O, Odabas MS. Changes in the contents of main secondary metabolites in two Turkish Hypericum species during plant development. Pharm Biol 2013; 51: 391-399
    CrossrefPubMedGoogle Scholar
  • 7 Fujimori K, Shibano M. Avicularin, a plant flavonoid, suppresses lipid accumulation through repression of C/EBPalpha-activated GLUT4-mediated glucose uptake in 3T3-L1 cells. J Agric Food Chem 2013; 61: 5139-5147
    CrossrefPubMedGoogle Scholar
  • 8 Shabana S, Kawai A, Kai K, Akiyama K, Hayashi H. Inhibitory activity against urease of quercetin glycosides isolated from Allium cepa and Psidium guajava . Biosci Biotechnol Biochem 2010; 74: 878-880
    CrossrefPubMedGoogle Scholar
  • 9 Vo VA, Lee JW, Chang JE, Kim JY, Kim NH, Lee HJ, Kim SS, Chun W, Kwon YS. Avicularin Inhibits Lipopolysaccharide-Induced Inflammatory Response by Suppressing ERK Phosphorylation in RAW 264.7 Macrophages. Biomol Ther (Seoul) 2012; 20: 532-537
    CrossrefPubMedGoogle Scholar
  • 10 Zhang WM, Li RF, Sun M, Hu DM, Qiu JF, Yan YH. UPLC-MS/MS method for determination of avicularin in rat plasma and its application to a pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci 2014; 965: 107-111
    CrossrefPubMedGoogle Scholar
  • 11 Goldman R. Endogenous creatinine clearance by rats. Proc Soc Exp Biol Med 1967; 125: 1021-1024
    CrossrefPubMedGoogle Scholar
  • 12 Zhao M, Xu J, Qian D, Guo J, Jiang S, Shang EX, Duan JA, Yang J, Du LY. Ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry for determination of avicularin metabolites produced by a human intestinal bacterium. J Chromatogr B Analyt Technol Biomed Life Sci 2014; 949–950: 30-36
    PubMedGoogle Scholar
  • 13 Davis B, Morris T. Commentary: physiological parameters in laboratory animals and humans. Pharm Res 1993; 10: 1093-1095
    CrossrefPubMedGoogle Scholar
  • 14 Yu M, Salvador LA, Sy SK, Tang Y, Singh RS, Chen QY, Liu Y, Hong J, Derendorf H, Luesch H. Largazole pharmacokinetics in rats by LC-MS/MS. Mar Drugs 2014; 12: 1623-1640
    CrossrefPubMedGoogle Scholar
  • 15 Sy SK, Malmberg R, Matsushima A, Asin-Prieto E, Rosenkranz B, Cotton MF, Derendorf H, Innes S. Effect of reducing the paediatric stavudine dose by half: a physiologically-based pharmacokinetic model. Int J Antimicrob Agents DOI: 10.1016/j.ijantimicag.2014.12.016. advance online publication 2015 Jan 19
    PubMedGoogle Scholar
  • 16 Sharma V, McNeill JH. To scale or not to scale: the principles of dose extrapolation. Br J Pharmacol 2009; 157: 907-921
    CrossrefPubMedGoogle Scholar
  • 17 Wojcikowski K, Gobe G. Animal studies on medicinal herbs: predictability, dose conversion and potential value. Phytother Res 2014; 28: 22-27
    CrossrefPubMedGoogle Scholar
  • 18 Sy SK, Asin-Prieto E, Derendorf H, Samara E. Predicting pediatric age-matched weight and body mass index. AAPS J 2014; 16: 1372-1379
    CrossrefPubMedGoogle Scholar
  • 19 Mahmood I. Role of fixed coefficients and exponents in the prediction of human drug clearance: how accurate are the predictions from one or two species?. J Pharm Sci 2009; 98: 2472-2493
    CrossrefPubMedGoogle Scholar
  • 20 Huang Q, Gehring R, Tell LA, Li M, Riviere JE. Interspecies allometric meta-analysis of the comparative pharmacokinetics of 85 drugs across veterinary and laboratory animal species. J Vet Pharmacol Ther DOI: 10.1111/jvp.12174. advance online publication 2014 Oct 21
    PubMedGoogle Scholar
  • 21 Huang Q, Riviere JE. The application of allometric scaling principles to predict pharmacokinetic parameters across species. Expert Opin Drug Metab Toxicol 2014; 10: 1241-1253
    CrossrefPubMedGoogle Scholar
  • 22 Nagilla R, Ward KW. A comprehensive analysis of the role of correction factors in the allometric predictivity of clearance from rat, dog, and monkey to humans. J Pharm Sci 2004; 93: 2522-2534
    CrossrefPubMedGoogle Scholar
  • 23 Mahmood I. Application of fixed exponent 0.75 to the prediction of human drug clearance: an inaccurate and misleading concept. Drug Metabol Drug Interact 2009; 24: 57-81
    CrossrefPubMedGoogle Scholar
  • 24 Dost T, Ozkayran H, Gokalp F, Yenisey C, Birincioglu M. The effect of Hypericum perforatum (St. Johnʼs Wort) on experimental colitis in rat. Dig Dis Sci 2009; 54: 1214-1221
    CrossrefPubMedGoogle Scholar
  • 25 Rodrigues ED, da Silva DB, de Oliveira DC, da Silva GV. DOSY NMR applied to analysis of flavonoid glycosides from Bidens sulphurea . Magn Reson Chem 2009; 47: 1095-1100
    CrossrefPubMedGoogle Scholar
  • 26 Silva DB. Atividade antialérgica e estudos químicos das espécies Bidens gardneri Bak. e Bidens sulphurea (Cav.) Sch. Bip. (Asteraceae) [dissertation]. Ribeirão Preto: Universidade de São Paulo; 2009: 408
    PubMedGoogle Scholar
  • 27 Shu JC, Chou GX, Wang ZT. One new diphenylmethane glycoside from the leaves of Psidium guajava L. Nat Prod Res 2012; 26: 1971-1975
    CrossrefPubMedGoogle Scholar
  • 28 Matuszewski BK, Constanzer ML, Chavez-Eng CM. Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal Chem 2003; 75: 3019-3030
    CrossrefPubMedGoogle Scholar
  • 29 Marchi I, Viette V, Badoud F, Fathi M, Saugy M, Rudaz S, Veuthey JL. Characterization and classification of matrix effects in biological samples analyses. J Chromatogr A 2010; 1217: 4071-4078
    CrossrefPubMedGoogle Scholar
  • 30 Diniz A, Escuder-Gilabert L, Lopes NP, Villanueva-Camanas RM, Sagrado S, Medina-Hernandez MJ. Characterization of interactions between polyphenolic compounds and human serum proteins by capillary electrophoresis. Anal Bioanal Chem 2008; 391: 625-632
    CrossrefPubMedGoogle Scholar
  • 31 Post TM, Freijer JI, Ploeger BA, Danhof M. Extensions to the visual predictive check to facilitate model performance evaluation. J Pharmacokinet Pharmacodyn 2008; 35: 185-202
    CrossrefPubMedGoogle Scholar