The Pharmacokinetics of Fentanyl in Intensive Care Patients

Summary

This study is part of a project intended to develop guidelines to optimise the dosing of fentanyl in intensive care patients. This study will focus on determining: * Whether the pharmacokinetics of fentanyl change during the ICU stay. * To what extent / the degree of change in fentanyl pharmacokinetics in ICU patients. * Which factors (e.g. physiological variables) that cause such a change. * Based on simulations, determine context-sensitive half-times of fentanyl in ICU patients.

Timeline

Start

2015-10

Primary completion

2017-09

Completion

2017-11

Publications

• Background Liu LL, Gropper MA. Postoperative analgesia and sedation in the adult intensive care unit: a guide to drug selection. Drugs. 2003;63(8):755-67. doi: 10.2165/00003495-200363080-00003.
• Background Wagner BK, O'Hara DA. Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of agitated critically ill patients. Clin Pharmacokinet. 1997 Dec;33(6):426-53. doi: 10.2165/00003088-199733060-00003.
• Background Gehlbach BK, Kress JP. Sedation in the intensive care unit. Curr Opin Crit Care. 2002 Aug;8(4):290-8. doi: 10.1097/00075198-200208000-00004.
• Background Hogarth DK, Hall J. Management of sedation in mechanically ventilated patients. Curr Opin Crit Care. 2004 Feb;10(1):40-6. doi: 10.1097/00075198-200402000-00007.
• Background Patel SB, Kress JP. Sedation and analgesia in the mechanically ventilated patient. Am J Respir Crit Care Med. 2012 Mar 1;185(5):486-97. doi: 10.1164/rccm.201102-0273CI. Epub 2011 Oct 20.
• Background Puntillo KA, Arai S, Cohen NH, Gropper MA, Neuhaus J, Paul SM, Miaskowski C. Symptoms experienced by intensive care unit patients at high risk of dying. Crit Care Med. 2010 Nov;38(11):2155-60. doi: 10.1097/CCM.0b013e3181f267ee.
• Background Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013 Jan;41(1):263-306. doi: 10.1097/CCM.0b013e3182783b72.
• Background Fukuda K. Intravenous opioid anesthetics. In Anesthesia, 6th Ed (ed Miller RD), Elsevier Churchill Livingstone, Philadelphia, pp 379-437
• Background Katz R, Kelly HW. Pharmacokinetics of continuous infusions of fentanyl in critically ill children. Crit Care Med. 1993 Jul;21(7):995-1000. doi: 10.1097/00003246-199307000-00012.
• Background Frenkel C, Schuttler J, Ihmsen H, Heye H, Rommelsheim K. Pharmacokinetics and pharmacodynamics of propofol/alfentanil infusions for sedation in ICU patients. Intensive Care Med. 1995 Dec;21(12):981-8. doi: 10.1007/BF01700659.
• Background Ethuin F, Boudaoud S, Leblanc I, Troje C, Marie O, Levron JC, Le Moing JP, Assoune P, Eurin B, Jacob L. Pharmacokinetics of long-term sufentanil infusion for sedation in ICU patients. Intensive Care Med. 2003 Nov;29(11):1916-20. doi: 10.1007/s00134-003-1920-y. Epub 2003 Aug 16.
• Background Hughes MA, Glass PS, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 1992 Mar;76(3):334-41. doi: 10.1097/00000542-199203000-00003.
• Background Shafer SL, Varvel JR. Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology. 1991 Jan;74(1):53-63. doi: 10.1097/00000542-199101000-00010.
• Background Vuyk J, Mertens MJ, Olofsen E, Burm AG, Bovill JG. Propofol anesthesia and rational opioid selection: determination of optimal EC50-EC95 propofol-opioid concentrations that assure adequate anesthesia and a rapid return of consciousness. Anesthesiology. 1997 Dec;87(6):1549-62. doi: 10.1097/00000542-199712000-00033. No abstract available.
• Background Ourahma S, Marchetti F, Clergue F, Levron JC, Le Moing JP, Viars P. [Peroperative perfusion of fentanyl or sufentanil: plasma concentrations and postoperative respiratory changes]. Ann Fr Anesth Reanim. 1993;12(4):357-64. doi: 10.1016/s0750-7658(05)80101-7. French.
• Background Dean M. Opioids in renal failure and dialysis patients. J Pain Symptom Manage. 2004 Nov;28(5):497-504. doi: 10.1016/j.jpainsymman.2004.02.021.
• Background Joh J, Sila MK, Bastani B. Nondialyzability of fentanyl with high-efficiency and high-flux membranes. Anesth Analg. 1998 Feb;86(2):447. doi: 10.1097/00000539-199802000-00049. No abstract available.
• Background Feierman DE, Lasker JM. Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. Role of CYP3A4. Drug Metab Dispos. 1996 Sep;24(9):932-9.
• Background Labroo RB, Paine MF, Thummel KE, Kharasch ED. Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implications for interindividual variability in disposition, efficacy, and drug interactions. Drug Metab Dispos. 1997 Sep;25(9):1072-80.
• Background Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J, Watkins PB, Daly A, Wrighton SA, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Venkataramanan R, Strom S, Thummel K, Boguski MS, Schuetz E. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet. 2001 Apr;27(4):383-91. doi: 10.1038/86882.
• Background Takashina Y, Naito T, Mino Y, Yagi T, Ohnishi K, Kawakami J. Impact of CYP3A5 and ABCB1 gene polymorphisms on fentanyl pharmacokinetics and clinical responses in cancer patients undergoing conversion to a transdermal system. Drug Metab Pharmacokinet. 2012;27(4):414-21. doi: 10.2133/dmpk.dmpk-11-rg-134. Epub 2012 Jan 24.
• Background Wright PM. Population based pharmacokinetic analysis: why do we need it; what is it; and what has it told us about anaesthetics? Br J Anaesth. 1998 Apr;80(4):488-501. doi: 10.1093/bja/80.4.488. No abstract available.
• Background Segredo V, Caldwell JE, Wright PM, Sharma ML, Gruenke LD, Miller RD. Do the pharmacokinetics of vecuronium change during prolonged administration in critically ill patients? Br J Anaesth. 1998 Jun;80(6):715-9. doi: 10.1093/bja/80.6.715.

Drugs

Indications