Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000058.xml
CC BY-NC-ND 4.0 · Planta Med 2023; 89(02): 194-207
DOI: 10.1055/a-1829-9546
DOI: 10.1055/a-1829-9546
Biological and Pharmacological Activity
Original Papers
Placental Passage of Protopine in an Ex Vivo Human Perfusion System
Supported by: Swiss National Science Foundation Sinergia project CRSII5_177260
Abstract
The placental passage of protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. The study compound did not affect placental viability or functionality, as glucose consumption, lactate production, and beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings.
Key words
Protopine - Eschscholzia californica - Papaveraceae - placental barrier - ex vivo cotyledon perfusion - pregnancy** Present address: Oncodesign SA, Villebon-sur-Yvette, France
Supporting Information
- Supporting Information
Perfusion profiles of all study compounds with absolute concentrations (ng/mL), compound recoveries, fraction unbound of compounds to the placental homogenate, homogenate matrix effects, perfusion profile of antipyrine from control perfusions, characteristics of placentae used, data from individual perfusions in detail, assessment of the suitability of a fetal capillary integrity marker, and details on the U(H)PLC-MS/MS bioanalytical methods are available as Supporting Information.
Publication History
Received: 02 March 2022
Accepted after revision: 08 April 2022
Accepted Manuscript online:
20 April 2022
Article published online:
22 August 2022
© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Gedeon C, Koren G. Designing pregnancy centered medications: Drugs which do not cross the human placenta. Placenta 2006; 27: 861-868
- 2 Abduljalil K, Badhan RKS. Drug dosing during pregnancy – opportunities for physiologically based pharmacokinetic models. J Pharmacokinet Pharmacodyn 2020; 47: 319-340
- 3 Gupta M, Petsalis M, Powers K, Chen HY, Chauhan SP, Wagner S. Randomized clinical trials in obstetrics-gynecology registered at ClinicalTrials. gov: Characteristics and factors associated with publication. Eur J Obstet Gynecol Reprod Biol 2020; 251: 223-228
- 4 Swissmedic. Pregnancy, obstetrics and lactation. Medicines for pregnant and breastfeeding women. 2017. Accessed April 8, 2021 at: https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/market-surveillance/fokusthemen/pregnancy-breastfeeding.html
- 5 Bornhauser CB, Quack Lötscher KC, Seifert B, Simões-Wüst AP. Diet, medication use and drug intake during pregnancy: Data from the consecutive Swiss Health Surveys of 2007 and 2012. Swiss Med Wkly 2017; 147: w14572
- 6 Randecker E, Gantner G, Spiess D, Quack Lötscher KC, Simões-Wüst AP. What pregnant women are taking: Learning from a survey in the Canton of Zurich. 2020. Accessed April 13, 2021 at: https://smw.ch/op-eds/post/what-pregnant-women-are-taking-learning-from-a-survey-in-the-canton-of-zurich
- 7 Kennedy DA, Lupattelli A, Koren G, Nordeng H. Herbal medicine use in pregnancy: Results of a multinational study. BMC Complem Altern M 2013; 13: 355
- 8 Berger A, Bachmann N, Signorell A, Erdin R, Oelhafen S, Reich O, Cignacco E. Perinatal mental disorders in Switzerland: Prevalence estimates and use of mental-health services. Swiss Med Wkly 2017; 147: w14417
- 9 Holst L, Wright D, Haavik S, Nordeng H. Safety and efficacy of herbal remedies in obstetrics – review and clinical implications. Midwifery 2011; 27: 80-86
- 10 Rolland A, Fleurentin J, Lanhers MC, Younos C, Misslin R, Mortier F, Pelt JM. Behavioural effects of the American traditional plant Eschscholzia californica: Sedative and anxiolytic properties. Planta Med 1991; 57: 212-216
- 11 European Medicines Agency. EMA/HMPC/680372/2013 – European Union herbal monograph on Eschscholzia californica Cham., herba. 2015. Accessed November 23, 2021 at: https://www.ema.europa.eu/en/documents/herbal-monograph/final-european-union-herbal-monograph-eschscholzia-californica-cham-herba_en.pdf
- 12 European Medicines Agency. EMA/HMPC/680375/2013 – Assessment report on Eschscholzia californica Cham., herba. 2015. Accessed November 23, 2021 at: https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-eschscholzia-californica-cham-herba_en.pdf
- 13 Medicinal product information search platform (AIPS). 2021. Accessed December 27, 2021 at: https://www.swissmedicinfo.ch
- 14 BʼOnaturis. Eschscholtzia BIO. Accessed April 9, 2021 at: https://www.bionaturis.ch/BIO-Kapseln/Eschscholtzia-BIO-225-mg-120-Kapseln.html
- 15 Guinaudeau H, Shamma M. The protopine alkaloids. J Nat Prod 1982; 45: 237-246
- 16 Guédon D, Cappelaere N, Simanek V. HPLC analysis of the main alkaloids from Eschscholtzia californica Cham. Phytochem Anal 1990; 1: 77-82
- 17 Tomè F, Colombo ML, Caldiroli L. A comparative investigation on alkaloid composition in different populations of Eschscholtzia californica Cham. Phytochem Anal 1999; 10: 264-267
- 18 Fedurco M, Gregorová J, Šebrlová K, Kantorová J, Peš O, Baur R, Sigel E, Táborská E. Modulatory effects of Eschscholzia californica alkaloids on recombinant GABAA receptors. Biochem Res Int 2015; 2015: 617620
- 19 Hanus M, Lafon J, Mathieu M. Double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders. Curr Med Res Opin 2004; 20: 63-71
- 20 Kardos J, Blasko G, Simonyi M. Enhancement of gamma-aminobutyric acid receptor binding by protopine-type alkaloids. Arzneimittelforschung 1986; 36: 939-940
- 21 Häberlein H, Tschiersch KP, Boonen G, Hiller KO. Chelidonium majus L.: Components with in vitro affinity for the GABAA receptor. Positive cooperation of alkaloids. Planta Med 1996; 62: 227-231
- 22 Gafner S, Dietz BM, McPhail KL, Scott IM, Glinski JA, Russell FE, McCollom MM, Budzinski JW, Foster BC, Bergeron C. Alkaloids from Eschscholzia californica and Their Capacity to Inhibit Binding of [3H]8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A Receptors in Vitro . J Nat 2006; 69: 432-435
- 23 Xu LF, Chu WJ, Qing XY, Li S, Wang XS, Qing GW, Fei J, Guo LH. Protopine inhibits serotonin transporter and noradrenaline transporter and has the antidepressant-like effect in mice models. Neuropharmacology 2006; 50: 934-940
- 24 Ala-Kokko T, Myllynen P, Vähäkangas K. Ex vivo perfusion of the human placental cotyledon: Implications for anesthetic pharmacology. Int J Obstet Anesth 2000; 9: 26-38
- 25 DʼErrico JN, Fournier SB, Stapleton PA. Ex vivo perfusion of the rodent placenta. Jove-J Vis Exp 2019; 147: e59412
- 26 Goeden N, Bonnin A. Ex vivo perfusion of mid-to-late-gestation mouse placenta for maternal-fetal interaction studies during pregnancy. Nat Protoc 2013; 8: 66-74
- 27 Leiser R, Kaufmann P. Placental structure: in a comparative aspect. Exp Clin Endocrinol 1994; 102: 122-134
- 28 van der Aa EM, Peereboom-Stegeman JHJC, Noordhoek J, Gribnau FWJ, Russel FGM. Mechanisms of drug transfer across the human placenta. Pharm World Sci 1998; 20: 139-148
- 29 Myllynen P, Vähäkangas K. Placental transfer and metabolism: An overview of the experimental models utilizing human placental tissue. Toxicol In Vitro 2013; 27: 507-512
- 30 Panigel M, Pascaud M, Brun JL. [Radioangiographic study of circulation in the villi and intervillous space of isolated human placental cotyledon kept viable by perfusion]. J Physiol (Paris) 1967; 59: 277
- 31 Malek A, Obrist C, Wenzinger S, von Mandach U. The impact of cocaine and heroin on the placental transfer of methadone. Reprod Biol Endocrin 2009; 7: 61
- 32 Grafmüller S, Manser P, Krug HF, Wick P, von Mandach U. Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model. Jove-J Vis Exp 2013; 76: e50401
- 33 Vähäkangas K, Myllynen P. Experimental methods to study human transplacental exposure to genotoxic agents. Mutat Res 2006; 608: 129-135
- 34 Hutson J, Garcia-Bournissen F, Davis A, Koren G. The human placental perfusion model: A systematic review and development of a model to predict in vivo transfer of therapeutic drugs. Clin Pharmacol Ther 2011; 90: 67-76
- 35 Manda VK, Ibrahim MA, Dale OR, Kumarihamy M, Cutler SJ, Khan IA, Walker LA, Muhammad I, Khan SI. Modulation of CYPs, P-gp, and PXR by Eschscholzia californica (California Poppy) and Its Alkaloids. Planta Med 2016; 82: 551-558
- 36 Heikkinen T, Ekblad U, Laine K. Transplacental transfer of citalopram, fluoxetine and their primary demethylated metabolites in isolated perfused human placenta. BJOG 2002; 109: 1003-1008
- 37 Myllynen P, Vahakangas K. An examination of whether human placental perfusion allows accurate prediction of placental drug transport: studies with diazepam. J Pharmacol Toxicol 2002; 48: 131-138
- 38 Schneider H, Dancis J, Panigel M. Transfer across perfused human placenta of antipyrine, sodium, and leucine. Am J Obstet Gynecol 1972; 114: 822-828
- 39 Spiess D, Winker M, Chauveau A, Abegg VF, Potterat O, Hamburger M, Gründemann C, Simões-Wüst AP. Medicinal plants for the treatment of mental diseases in pregnancy: An in vitro safety assessment. Planta Med 2021; DOI: 10.1055/a-1628-8132.
- 40 Malek A, Sager R, Lang AB, Schneider H. Protein transport across the in vitro perfused human placenta. Am J Reprod Immunol 1997; 38: 263-271
- 41 Malek A, Willi A, Müller J, Sager R, Hänggi W, Bersinger N. Capacity for hormone production of cultured trophoblast cells obtained from placentae at term and in early pregnancy. J Assist Reprod Gen 2001; 18: 299-304
- 42 Mathiesen L, Mose T, Morck TJ, Nielsen JK, Nielsen LK, Maroun LL, Dziegiel MH, Larsen LG, Knudsen LE. Quality assessment of a placental perfusion protocol. Reprod Toxicol 2010; 30: 138-146
- 43 Turowski G, Berge L, Helgadottir L, Jacobsen EM, Roald B. A new, clinically oriented, unifying and simple placental classification system. Placenta 2012; 33: 1026-1035
- 44 Khong TY, Mooney EE, Ariel I, Balmus NC, Boyd TK, Brundler MA, Derricott H, Evans MJ, Faye-Petersen OM, Gillan JE. Sampling and definitions of placental lesions: Amsterdam placental workshop group consensus statement. Arch Pathol Lab Med 2016; 140: 698-713
- 45 U.S. Food and Drug Administration. Bioanalytical method validation: Guidance for industry. 2018. Accessed March 18, 2021 at: https://www.fda.gov/files/drugs/published/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf
- 46 European Medicines Agency. EMA/CHMP/ICH/172948/2019 – ICH guideline M10 on bioanalytical method validation. 2019. Accessed April 28, 2021 at: https://www.ema.europa.eu/en/documents/scientific-guideline/draft-ich-guideline-m10-bioanalytical-method-validation-step-2b_en.pdf
- 47 Riccardi K, Ryu S, Tess D, Li R, Luo L, Johnson N, Jordan S, Patel R, Di L. Comparison of fraction unbound between liver homogenate and hepatocytes at 4 °C. AAPS J 2020; 22: 91