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The pharmacokinetics and pharmacodynamics of cisatracurium in critically ill patients with severe sepsis.

AbstractAIM:
To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium in critically ill patients with severe sepsis.
METHODS:
Blood samples were collected before and over 8 h after a single bolus dose of cisatracurium 0.1 mg kg(-1) . Neuromuscular block was assessed by accelerometric peripheral nerve stimulation (TOF Watch). Plasma concentration and neuromuscular block data were fitted using population analysis.
RESULTS:
Steady-state volume of distribution was determined to be 111 ± 71 ml kg(-1) and plasma clearance was 5.2 ± 1.8 ml min(-1) kg(-1) in these patients with greater inter-patient variability compared with other populations. The time to maximum block (8.3 ± 2.9 min) and delay time of transferring from central to effect compartment (17.2 min) was much longer, while the maximum block (95.0 ± 6.3%) was less compared with those in other patient populations. The effect compartment concentration resulting in 50% of maximum effect (128 ± 58 ng ml(-1)) was larger than previously described.
CONCLUSIONS:
This study suggests that standard dosing of cisatracurium in patients with severe sepsis results in a slower patient response with a reduced effect. Use of a larger dose may overcome this reduced delayed response.
AuthorsXin Liu, Peter S Kruger, Michael Weiss, Michael S Roberts
JournalBritish journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 73 Issue 5 Pg. 741-9 (May 2012) ISSN: 1365-2125 [Electronic] England
PMID22114771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
Chemical References
  • Neuromuscular Blocking Agents
  • Atracurium
  • cisatracurium
Topics
  • Adult
  • Aged
  • Atracurium (analogs & derivatives, pharmacokinetics, pharmacology)
  • Critical Illness
  • Dose-Response Relationship, Drug
  • Drug Resistance
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • Neuromuscular Blocking Agents (pharmacokinetics, pharmacology)
  • Sepsis (drug therapy, metabolism)
  • Severity of Illness Index
  • Time Factors

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