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PLoS One. 2018 Nov 14;13(11):e0207427. doi: 10.1371/journal.pone.0207427. eCollection 2018.

The pharmacokinetics of dexmedetomidine in patients with obstructive jaundice: A clinical trial.

Author information

1
Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
2
Department of Anesthesiology, Shanghai Shuguang Hospital, University of Traditional Chinese Medicine, Shanghai, China.
3
Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

OBJECTIVES:

Dexmedetomidine, a highly selective central α2-agonist, undergoes mainly biotransformation in the liver. The pharmacokinetics of dexmedetomidine were significantly affected by hepatic insufficiency. The clearance of dexmedetomidine in patients with severe hepatic failure decreased by 50% compared with controls. We tested the hypothesis that the pharmacokinetics of dexmedetomidine would be affected by obstructive jaundice. The prospective registration number of clinical trial is ChiCTR-IPR-15007572.

METHODS:

18 patients with obstructive jaundice and 12 non-jaundiced patient controls received dexmedetomidine, 1 μg/kg, over 10 min. Arterial blood samples were drawn before, during, and up to 5 h after the infusion. Plasma dexmedetomidine concentrations were determined by 1290 infinity high performance liquid chromatography coupled with 6470 tandem mass spectrometry. The relevant pharmacokinetic parameters were calculated by non-compartmental analysis using Phoenix WinNonlin 7.0.

RESULTS:

Plasma clearance of dexmedetomidine was decreased by 33.3% in the obstructive jaundice group as compared with the control group (0.0068±0.0017 vs. 0.0102±0.0033 L/kg/min; P = 0.002). Volume of distribution was decreased by 29.2% in the obstructive jaundice group as compared with the control group (1.43±0.58 vs. 2.02±0.84 L/kg; P = 0.041).

CONCLUSIONS:

This study demonstrates that the clearance and distribution volume of dexmedetomidine were decreased in patients with obstructive jaundice. It may be advisable to adjust the dose of dexmedetomidine in those patients.

PMID:
30427948
PMCID:
PMC6235379
DOI:
10.1371/journal.pone.0207427
[Indexed for MEDLINE]
Free PMC Article

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