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

Authors :
Hai-Bo Qiu
Mei-Hua Cai
Jin-Chao Song
Zhi-Jie Lu
Qian-Bo Chen
Hao Gao
M. Z. Zhang
Source :
PLoS ONE, Vol 13, Iss 11, p e0207427 (2018), PLoS ONE
Publication Year :
2018
Publisher :
Public Library of Science (PLoS), 2018.

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.

Details

ISSN :
19326203
Volume :
13
Database :
OpenAIRE
Journal :
PLOS ONE
Accession number :
edsair.doi.dedup.....466e0e08d68da13fb99b7d900a82dad2