Population Pharmacokinetics of Etomidate Isnotchanged in Patients With Obstructive Jaundice: An Observational Study

Background: Etomidate is a commonly used in induction of anesthesia. We have previously confirmed that etomidate requirements are significantly reduced in patients with obstructive jaundice and that etomidate anesthesia during ERCP results in more stable hemodynamics when compared with propofol. The aim of the present study is to investigate the pharmacokinetics of etomidate in patientswith and without obstructive jaundice. Method: 18 patients with obstructive jaundice and 12 non-jaundiced patients scheduled for bile duct surgery were enrolled in the study. Etomidate 0.333 mg/kg was administered by IV bolus for anesthetic induction. Arterial blood samples were drawn before, during, and up to 300 minutes after bolus. Plasma etomidate concentrations were determined using a validated high-performance liquid chromatography tandem mass spectrometry assay. A population nonlinear mixed-effects modeling approach was used to characterize etomidate pharmacokinetics. Thecovariates age, gender, height, weight, body surface area (BSA), body mass index (BMI), lean body mass (LBM), total bilirubin (TBL), alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid (TBA), creatinine(CR), blood urea nitrogen(BUN)were tested for significant effects on parametersusing a multiple forward selection approach. Covariate effects were judged based onchanges in the objective function value (OFV). Results: : A three-compartment disposition model adequately described the pharmacokinetics of etomidate.The model was further improved when height was a covariate of total clearance [Cl 1 =1.30+0.0232(HT-162), ΔOFV=−7.33; P 0.01). For the height of 162cm, the final pharmacokinetic parameter valueswere as follows:V1=1.42 (95% CI, 1.01-1.83, L), V2=5.52 (95% CI, 4.07-6.97, L),V3=63.9 (95% CI, 41.95-85.85, L),Cl1= 1.30 (95% CI, 1.19-1.41, l/min), Cl2= 1.21 (95%CI, 0.95-1.47, L/min),and Cl3=0.584 (95%CI, 0.95-1.21, L/min), respectively, respectively. Conclusion: A 3-compartment open model might best describe the concentration profile of etomidate after bolus infusion for anesthesia induction. The pharmacokinetics of etomidate has not been changed in the obstructive jaundice. Trial registration: The trial was registered prior to patient enrollment at clinicaltrials.gov (ChiCTR-IPR-15007574, Principal investigator: Jin-chao Song, Date of registration: 2015-12-10).