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Pharmakologische Aspekte der intrauterinen Drogenexposition und klinische Konsequenzen

  • Bernhard Roth

Zusammenfassung

Ein neonatales Abstinenzsyndrom (NAS) tritt bei etwa 50–90% der Neugeborenen auf, die vorgeburtlich über längere Zeit hinweg Opioiden ausgesetzt waren [15]. Während der letzten Jahre hat sich die Häufi gkeit des NAS deutlich erhöht. In den USA stieg von 2004 bis 2013 die Rate von Neugeborenen, die mit einem NAS auf einer neonatologischen Intensivstation aufgenommen worden waren, von 17 auf 27 pro 1000 Aufnahmen [36]. Parallel dazu nahm die Behandlungsdauer auf der Intensivstation deutlich zu und ebenso der Anteil der Neugeborenen, die eine pharmakologische Th erapie des Abstinenzsyndroms erhielten.

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Literatur

  1. 1.
    Abduljalil K, Furness P, Johnson TN et al. Anatomical, physiological and metabolic changes with gestational age during normal pregnancy: a database for parameters required in physiologically based pharmacokinetic modelling. Clin Pharmacokinet 2012; 51: 365–396.CrossRefGoogle Scholar
  2. 2.
    Allegaert K, Vanhaesebrouck S, Verbesselt R et al. In vivo glucuronidation activity of drugs in neonates: extensive interindividual variability despite their young age. Ther Drug Monit 2009; 31: 411–415.CrossRefGoogle Scholar
  3. 3.
    Anand KJ, Anderson BJ, Holford NH et al. Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial. Br J Anaesth 2008; 105: 680–689.CrossRefGoogle Scholar
  4. 4.
    Dancis J, Braverman N, Lind J. Plasma protein synthesis in the human fetus and placenta. J Clin Invest 1957; 36: 398–404.CrossRefGoogle Scholar
  5. 5.
    Daood MJ, Tsai C, Ahdab-Barmada M et al. ABC transporter (Pgp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS. Neuropediatrics 2008; 39: 11–18.CrossRefGoogle Scholar
  6. 6.
    de Castro A, Jones HE, Johnson RE et al. Methadone, cocaine, opiates and metabolite dispositions in umbilical cord and correlations to maternal methadone dose and neonatal outcomes. Ther Drug Monit 2011; 33: 443–452.Google Scholar
  7. 7.
    de Castro A, Jones HE, Johnson RE et al. Maternal methadone dose, placental methadone concentrations, and neonatal outcomes. Clin Chem 2011; 57: 449–458.Google Scholar
  8. 8.
    Ekström L, Johansson M, Rane A. Tissue distribution and relative gene expression of UDP-Glucuronosyl transferases (2B7, 2B15, 2B17) in the human fetus. Drug Metab Disp 2013; 41: 291–295.CrossRefGoogle Scholar
  9. 9.
    Elkader A, Sproule B. Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokinet 2005; 44: 661–680.CrossRefGoogle Scholar
  10. 10.
    Fokina VM, Patrikeeva SL, Zharikova L et al. Transplancental transfer and metabolism of buprenorphine in preterm human placenta. Am J Perinatol 2011; 28: 25–32.CrossRefGoogle Scholar
  11. 11.
    Fukuda T, Chidamboran V, Mizuno T et al. OCT1 genetic variants influence the pharmacokinetics of morphine in children. Pharmacogenomics 2013; 14: 1141–1151.CrossRefGoogle Scholar
  12. 12.
    Hakkola J, Pasanen M, Hukkanen J et al. Expression of xenobiotic – metabolizing cytochrome P450 forms in human fullterm placenta. Biochem Pharmacol 1996; 51: 403–411.Google Scholar
  13. 13.
    Hartley R, Green M, Quinn MW. Development of morphine glucuronidation in premature neonates. Biol Neonate 1994; 66: 1–9.CrossRefGoogle Scholar
  14. 14.
    Hieronymus TL, Nanovskaya TN, Deshmukh SV et al. Methadone metabolism by early gestational age placentas. Am J Perinatol 2006; 23: 287–294.CrossRefGoogle Scholar
  15. 15.
    Hudak ML, Tan RC, The Committee on Drugs, the Commitee on Fetus and Newborn. Neonatal drug withdrawal. Pediatrics 2012; 129: e540–560.Google Scholar
  16. 16.
    Iqbal M, Audette MC, Petropoulos S. Placental drug transporters and their role in fetal protection. Placenta 2012; 33: 137–142.CrossRefGoogle Scholar
  17. 17.
    Isokerranen N, Thummel KE. Drug metabolism and transport during pregnancy: How does drug disposition change during pregnancy and what are the mechanisms that cause such changes? Drug Metab Disp 2013; 41: 256–262.Google Scholar
  18. 18.
    Jones HE, Johnson RE, Jasinski DR et al. Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Drug and Alcohol Dependence 2005; 79: 1–10.CrossRefGoogle Scholar
  19. 19.
    Jones HE, Kaltenbach K, Heil SH et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. NEJM 2010; 363: 2320–2331.CrossRefGoogle Scholar
  20. 20.
    Kearns GL, Abdel-Rahman SM, Alander SW et al. Developmental pharmacology – drug disposition, action, and therapy in infants and children. NEJM 2003; 349: 1157–1167.CrossRefGoogle Scholar
  21. 21.
    Knibbe CA, Krekels EH, van den Anker JN et al. Morphine glucuronidation in preterm neonates, infants and children younger than 3 years. Clin Pharmacokinet 2009; 48: 371–385.CrossRefGoogle Scholar
  22. 22.
    Koren G. Changes in drug disposition in pregnancy and their clinical implications. In: Koren G (ed.): Maternal-fetal toxicology. 2nd ed. New York: Marcel Dekker, 1994, pp 1–13.Google Scholar
  23. 23.
    Lam J, Koren G. P-glycoprotein in the developing brain: A review of the effects of ontogeny on the safety of opioids in neonates. Ther Drug Monit 2014; 36: 699–705.Google Scholar
  24. 24.
    Lejeune C, Simmat-Durand L, Gouraier L et al. Prospective multicenter observational study of 260 infants born to 259 opiatedependent mothers on methadone or high-dose buprenorphine substitution. Drug and Alcohol Dependence 2006; 82: 250–257.CrossRefGoogle Scholar
  25. 25.
    Lewis T, Dinh J, Leeder JS. Genetic determinants of fetal opiate exposure and risk of neonatal abstinence syndrome: knowledge deficites and prospects for future research. Clin Pharmacol Ther 2015; 98: 309–320.CrossRefGoogle Scholar
  26. 26.
    Loebstein R, Lalkin A, Koren G. Pharmacokinetic changes during pregnancy and their relevance. Clin Pharmacokinet 1997; 33: 328–343.Google Scholar
  27. 27.
    Malek A, Obrist C, Wentzinger S et al. The impact of cocaine and heroin on the placental transfer of methadone. Reprod Biol Endocrinol 2009; 7: 61.CrossRefGoogle Scholar
  28. 28.
    Matic M, van den Bosch GE, de Wildt SN et al. Genetic variants associated with thermal pain sensitivity in a pediatric population. Pain 2016; 157: 2476–2482.CrossRefGoogle Scholar
  29. 29.
    Miller RK, Kostalka TR, Brent RL. The transport of molecules across placental membranes. In: Poste G, Nicolson GL (eds.): The cell surface in animal embryogenesis and development. Amsterdam, New York, Oxford: North-Holland Publishing, 1976, pp 145–223.Google Scholar
  30. 30.
    Mooij MG, Nies AT, Knibbe CA et al. Development of human membrane transporters: drug disposition and pharmacogenetics. Clin Pharmacokinet 2016; 55: 507–524.CrossRefGoogle Scholar
  31. 31.
    Nanovskaya TN, Deshmukh SV, Nekhayeva IA et al. Methadone metabolism by human placenta. Biochem Pharmacol 2004; 68: 583–591.CrossRefGoogle Scholar
  32. 32.
    Nekhyeva IA, Nanovskaya TN, Hankins GO et al. Role of human placental efflux transporter P-glycoprotein in the transfer of buprenorphine, levo-alpha-acetyl-methadol, and paclitaxel. Am J Perinatol 2006; 23: 423–430.Google Scholar
  33. 33.
    Pasanen M, Pelkonen O. The expression and environmental regulation of P450 enzymes in human placenta. Crit Rev Toxicol 1994; 24: 211–229.CrossRefGoogle Scholar
  34. 34.
    Seligman NS, Almario CV, Hayes EJ et al. Relationship between maternal methadone dose at delivery and neonatal abstinence syndrome. J Pediatr 2010; 157: 428–433.CrossRefGoogle Scholar
  35. 35.
    Sun M, Kingdom J, Baczyk D et al. Expression of the multidrug resistance P-glycoprotein (ABCB1 glycoprotein) in human placenta decreases with advancing gestation. Placenta 2006; 27: 602–609.CrossRefGoogle Scholar
  36. 36.
    Tolia VN, Patrick SW, Bennett MM et al. Increasing incidence of the neonatal abstinence syndrome in U. S. Neonatal ICUs. NEJM 2015; 372: 2118–2126.CrossRefGoogle Scholar
  37. 37.
    Tracy TS, Venkataramanan R, Glover DD et al. Temporal changes in drug metabolism (CYP1A2, CYP206 and CYP3A activity) during pregnancy. Am J Obstet Gynecol 2005; 192: 633–639.CrossRefGoogle Scholar
  38. 38.
    Tzvetkov MV, dos Santos Pereira, Meineke I et al. Morphine is a substrate of the organic cation transporter OCT1 and polymorphism in OCT1 gene affect morphine pharmacokinetics after codeine administration. Biochemical Pharmacology 2013; 86: 666–678.CrossRefGoogle Scholar
  39. 39.
    Wachman EM, Hayes MJ, Brown MS et al. Association of OPRM1 and COMT single-nucleotide polymorphism with hospital length of stay and treatment of neonatal abstinence syndrome. JAMA 2013; 309: 1821–1827.CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH 2017

Authors and Affiliations

  • Bernhard Roth
    • 1
  1. 1.Klinik und Poliklinik für Kinder- und Jugendmedizin, Neonatologie und pädiatrische IntensivmedizinUniversitätsklinikum KölnKölnDeutschland

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