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Dexmedetomidin

Pharmakokinetik und Pharmakodynamik

Dexmedetomidine

Pharmacokinetics and pharmacodynamics

  • Klinische Pharmakologie
  • Published:
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Zusammenfassung

Mit Dexmedetomidin ist 2011 ein potenter selektiver α2-Adrenozeptor-Agonist zur Sedierung erwachsener, intensivmedizinisch behandelter Patienten neu auf dem europäischen Markt zugelassen worden. Dexmedetomidin zeigt konzentrationsabhängig sowohl sedierende als auch analgetische und anxiolytische Wirkungen. Aktuelle Studien lassen Dexmedetomidin als eine Alternative zu Midazolam für die Langzeitsedierung erscheinen. In dieser Übersichtsarbeit werden die pharmakokinetischen und pharmakodynamischen Eigenschaften von Dexmedetomidin insbesondere bei intensivmedizinischen Patienten, unter besonderer Berücksichtigung des Einflusses von Kovariaten, zusammengefasst. Obwohl Dexmedetomidin nur für Erwachsene zugelassen ist und die Anwendung bei Kindern daher einem „off label use“ entspricht, wird auch auf die Pharmakokinetik und -dynamik bei Kindern eingegangen, da dazu ebenfalls zahlreiche Studien vorliegen.

Abstract

Dexmedetomidine is a highly selective, potent α2-adrenoceptor agonist which was approved in 2011 by the European Medicines Agency for sedation of patients in intensive care units (ICU). Dexmedetomidine exhibits sedative as well as analgesic and anxiolytic effects. Recent studies suggest that dexmedetomidine may be an alternative to midazolam in long-term ICU sedation. This review summarizes the pharmacokinetics and pharmacodynamics of dexmedetomidine particularly in ICU patients and with special regard to covariate effects. Although dexmedetomidine is currently approved only for use in adults the pharmacokinetics and pharmacodynamics in children will also be addressed as there are numerous studies on this off-label use.

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Literatur

  1. Albrecht S, Ihmsen H, Hering W et al (1999) The effect of age on the pharmacokinetics and pharmacodynamics of midazolam. Clin Pharmacol Ther 65:630–639

    Article  PubMed  CAS  Google Scholar 

  2. Anttila M, Penttila J, Helminen A et al (2003) Bioavailability of dexmedetomidine after extravascular doses in healthy subjects. Br J Clin Pharmacol 56:691–693

    Article  PubMed  Google Scholar 

  3. Bach A, Motsch J, Schmidt H et al (1997) In-use contamination of propofol. A clinical study. Eur J Anaesthesiol 14:178–183

    Article  PubMed  CAS  Google Scholar 

  4. Blaine Easley R, Brady KM, Tobias JD (2007) Dexmedetomidine for the treatment of postanesthesia shivering in children. Paediatr Anaesth 17:341–346

    Article  Google Scholar 

  5. Buck ML (2010) Dexmedetomidine use in pediatric intensive care and procedural sedation. J Pediatr Pharmacol Ther 15:17–29

    PubMed  Google Scholar 

  6. Buhrer M, Mappes A, Lauber R et al (1994) Dexmedetomidine decreases thiopental dose requirement and alters distribution pharmacokinetics. Anesthesiology 80:1216–1227

    Article  PubMed  CAS  Google Scholar 

  7. Cortinez LI, Hsu YW, Sum-Ping ST et al (2004) Dexmedetomidine pharmacodynamics: Part II: crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology 101:1077–1083

    Article  PubMed  CAS  Google Scholar 

  8. Czaja AS, Zimmerman JJ (2009) The use of dexmedetomidine in critically ill children. Pediatr Crit Care Med 10:381–386

    Article  PubMed  Google Scholar 

  9. De Wolf AM, Fragen RJ, Avram MJ et al (2001) The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment. Anesth Analg 93:1205–1209

    Article  Google Scholar 

  10. Devlin JW, Lau AK, Tanios MA (2005) Propofol-associated hypertriglyceridemia and pancreatitis in the intensive care unit: an analysis of frequency and risk factors. Pharmacotherapy 25:1348–1352

    Article  PubMed  CAS  Google Scholar 

  11. Devlin JW, Mallow-Corbett S, Riker RR (2010) Adverse drug events associated with the use of analgesics, sedatives, and antipsychotics in the intensive care unit. Crit Care Med 38:231–243

    Article  Google Scholar 

  12. Diedrich DA, Brown DR (2011) Analytic reviews: propofol infusion syndrome in the ICU. J Intensive Care Med 26:59–72

    Article  PubMed  Google Scholar 

  13. Dutta S, Lal R, Karol MD et al (2000) Influence of cardiac output on dexmedetomidine pharmacokinetics. J Pharm Sci 89:519–527

    Article  PubMed  CAS  Google Scholar 

  14. Dyck JB, Maze M, Haack C et al (1993) Computer-controlled infusion of intravenous dexmedetomidine hydrochloride in adult human volunteers. Anesthesiology78:821–828

  15. Dyck JB, Maze M, Haack C et al (1993) The pharmacokinetics and hemodynamic effects of intravenous and intramuscular dexmedetomidine hydrochloride in adult human volunteers. Anesthesiology 78:813–820

    Article  PubMed  CAS  Google Scholar 

  16. Ebert TJ, Hall JE, Barney JA et al (2000) The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 93:382–394

    Article  PubMed  CAS  Google Scholar 

  17. Elvan EG, Oc B, Uzun S et al (2008) Dexmedetomidine and postoperative shivering in patients undergoing elective abdominal hysterectomy. Eur J Anaesthesiol 25:357–364

    Article  PubMed  CAS  Google Scholar 

  18. Fragen RJ (1997) Pharmacokinetics and pharmacodynamics of midazolam given via continuous intravenous infusion in intensive care units. Clin Ther 19:405–419, discussion 367–408

    Article  PubMed  CAS  Google Scholar 

  19. Hosokawa K, Shime N, Kato Y et al (2010) Dexmedetomidine sedation in children after cardiac surgery. Pediatr Crit Care Med 11:39–43

    Article  PubMed  Google Scholar 

  20. Huupponen E, Maksimow A, Lapinlampi P et al (2008) Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiol Scand 52:289–294

    Article  PubMed  CAS  Google Scholar 

  21. Iirola T, Ihmsen H, Laitio R et al (2012) Population pharmacokinetics of dexmedetomidine during long-term sedation in intensive care patients. Br J Anaesth 108:460–468

    Article  PubMed  CAS  Google Scholar 

  22. Iirola T, Vilo S, Aantaa R et al (2011) Dexmedetomidine inhibits gastric emptying and oro-caecal transit in healthy volunteers. Br J Anaesth 106:522–527

    Article  PubMed  CAS  Google Scholar 

  23. Jakob SM, Ruokonen E, Grounds RM et al (2012) Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 307:1151–1160

    Article  PubMed  CAS  Google Scholar 

  24. Jansson CC, Pohjanoksa K, Lang J et al (1999) Alpha2-adrenoceptor agonists stimulate high-affinity GTPase activity in a receptor subtype-selective manner. Eur J Pharmacol 374:137–146

    Article  PubMed  CAS  Google Scholar 

  25. Karol MD, Maze M (2000) Pharmacokinetics and interaction pharmacodynamics of dexmedetomidine in humans. Baillieres Best Pract Res Clin Anaesthesiol 14:261–269

    Article  CAS  Google Scholar 

  26. Kauppila T, Kemppainen P, Tanila H et al (1991) Effect of systemic medetomidine, an alpha 2 adrenoceptor agonist, on experimental pain in humans. Anesthesiology 74:3–8

    Article  PubMed  CAS  Google Scholar 

  27. Kharasch ED, Hill HF, Eddy AC (1991) Influence of dexmedetomidine and clonidine on human liver microsomal alfentanil metabolism. Anesthesiology 75:520–524

    Article  PubMed  CAS  Google Scholar 

  28. Kivisto KT, Kallio A, Neuvonen PJ (1994) Pharmacokinetics and pharmacodynamics of transdermal dexmedetomidine. Eur J Clin Pharmacol 46:345–349

    Article  PubMed  CAS  Google Scholar 

  29. Kohli U, Muszkat M, Sofowora GG et al (2010) Effects of variation in the human alpha2A- and alpha2C-adrenoceptor genes on cognitive tasks and pain perception. Eur J Pain 14:154–159

    Article  PubMed  CAS  Google Scholar 

  30. Lin L, Guo X, Zhang MZ et al (2011) Pharmacokinetics of dexmedetomidine in Chinese post-surgical intensive care unit patients. Acta Anaesthesiol Scand 55:359–367

    Article  PubMed  CAS  Google Scholar 

  31. Lin TF, Yeh YC, Lin FS et al (2009) Effect of combining dexmedetomidine and morphine for intravenous patient-controlled analgesia. Br J Anaesth 102:117–122

    Article  PubMed  CAS  Google Scholar 

  32. Link RE, Desai K, Hein L et al (1996) Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c. Science 273:803–805

    Article  PubMed  CAS  Google Scholar 

  33. Marsh B, White M, Morton N et al (1991) Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 67:41–48

    Article  PubMed  CAS  Google Scholar 

  34. Martin J, Franck M, Sigel S et al (2007) Changes in sedation management in German intensive care units between 2002 and 2006: a national follow-up survey. Crit Care 11:R124

    Article  PubMed  Google Scholar 

  35. Martin J, Parsch A, Franck M et al (2005) Practice of sedation and analgesia in German intensive care units: results of a national survey. Crit Care 9:R117–123

    Article  PubMed  Google Scholar 

  36. McKeage K, Perry CM (2003) Propofol: a review of its use in intensive care sedation of adults. CNS Drugs 17:235–272

    Article  PubMed  CAS  Google Scholar 

  37. Memis D, Dokmeci D, Karamanlioglu B et al (2006) A comparison of the effect on gastric emptying of propofol or dexmedetomidine in critically ill patients: preliminary study. Eur J Anaesthesiol 23:700–704

    Article  PubMed  CAS  Google Scholar 

  38. Muellejans B, Matthey T, Scholpp J et al (2006) Sedation in the intensive care unit with remifentanil/propofol versus midazolam/fentanyl: a randomised, open-label, pharmacoeconomic trial. Crit Care 10:R91

    Article  PubMed  Google Scholar 

  39. Nelson LE, Lu J, Guo T et al (2003) The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 98:428–436

    Article  PubMed  CAS  Google Scholar 

  40. Pichot C, Ghignone M, Quintin L (2012) Dexmedetomidine and clonidine: from second- to first-line sedative agents in the critical care setting? J Intensive Care Med 27:219–237

    Article  PubMed  CAS  Google Scholar 

  41. Potts AL, Anderson BJ, Warman GR et al (2009) Dexmedetomidine pharmacokinetics in pediatric intensive care–a pooled analysis. Paediatr Anaesth 19:1119–1129

    Article  PubMed  Google Scholar 

  42. Riker RR, Shehabi Y, Bokesch PM et al (2009) Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 301:489–499

    Article  PubMed  CAS  Google Scholar 

  43. Sessler CN, Gosnell MS, Grap MJ et al (2002) The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 166:1338–1344

    Article  PubMed  Google Scholar 

  44. Talke P, Richardson CA, Scheinin M, Fisher DM (1997) Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine. Anesth Analg 85:1136–1142

    PubMed  CAS  Google Scholar 

  45. Tan JA, Ho KM (2010) Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med 36:926–939

    Article  PubMed  CAS  Google Scholar 

  46. Venn RM, Bradshaw CJ, Spencer R et al (1999) Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 54:1136–1142

    Article  PubMed  CAS  Google Scholar 

  47. Venn RM, Grounds RM (2001) Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions. Br J Anaesth 87:684–690

    Article  PubMed  CAS  Google Scholar 

  48. Venn RM, Hell J, Grounds RM (2000) Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care 4:302–308

    Article  PubMed  CAS  Google Scholar 

  49. Venn RM, Karol MD, Grounds RM (2002) Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care. Br J Anaesth 88:669–675

    Article  PubMed  CAS  Google Scholar 

  50. Virtanen R, Savola JM, Saano V et al (1988) Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol 150:9–14

    Article  PubMed  CAS  Google Scholar 

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  1. Anästhesiologische Klinik, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Krankenhausstr. 12, 91054, Erlangen, Deutschland

    H. Ihmsen & T.I. Saari

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  1. H. Ihmsen
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  2. T.I. Saari
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Correspondence to H. Ihmsen.

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Ihmsen, H., Saari, T. Dexmedetomidin. Anaesthesist 61, 1059–1066 (2012). https://doi.org/10.1007/s00101-012-2114-1

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