Study On Pharmacokinetics Of Vecuronium In Recipients Of Liver Transplantation

Objective:1.To establish a method for the determination of vecuronium in human plasma using HPLC.2.To compare the pharmacokinetic parameter of vecuronium between the patients with their liver transplanted and those with their liver well-functioning.Method:1.Chromatographic conditions:Column:Kromasil C₁₈(250mm×4.6mm,5μm); Mobile phase:Methanol:0.02mol·L^-1Potassium dihydrogen phosphate solution(2:98 V/V),regulated with phosphate until pH=3.0.The mobile phase was added 1%(V/V) tetrahydrofuran,and filtrated by micro membranes of 0.45μm;UV detection wavelength:210nm;column temperature:room temperature;flow:1.0mL·min^-1; sensitivity:0.002(AUFS);sample injection volume:50μL。Samples:3mL Blood taken from patients was injected in a heparinization test-tube,which had been added 0.5mL 1mol·L^-1sodium dihydrogen phosphate solution.Then it was put into a B600-automatic high-speed centrifuge and centrifuged for 10min with 3000rpm.After centrifuged 500μL plasma of above sample was taken and mixed with 500μL ultra-pure water and 2mL chloroform for extraction(containing 5%isopropyl alcohol).Next,the mixture was mixed on a vortex mixer until balanced,and placed in a high-speed centrifuge to centrifuge for 5min.To repeat the extraction process for 3 times,then put it together,and blow-dry the mixture on 50℃water bath by N₂ stream.The residues dissolved by 200μL mobile phase.50μL sample was injected into the column.2.Pharmacokinetics.12 patients with liver transplant operation in Organ Transplant Center of Tianjin First Central Hospital and 12 patients with abdominal surgery(ASA1-2 level)or with general surgery were seleted randomly and respectively.Two groups of patients were injected 0.3mg scopolamine and 10mg diazepam intramuscularly.0.05mg·kg^-1midazolam,2mg·kg^-1propofol,5μg·kg^-1 fentanyl and 0.15mg·kg^-1vecuronium were injected intravenously.The maintainance dose of vecuronium is 0.lmg·kg^-1.The Muscle Relaxation Monitor was used to monitoring the muscle condition of patients.The time that T₁ restored to 20%was just the point of given drug next time.The plasma samples from control group, experimental group before liver transplantation and after liver transplantation were collected before the administration and at 2,5 30min after the first administration. The plasma concentrations were determinated and the pharmacokinetic parameters were calculated.Results:1.The linear range was 10⁴00μg·mL^-1.The detection limit was 10μg·mL^-1. The recovery(78.48±1.34%and 97.32±0.95%),the precision(4.19±0.77%and 4.66±1.72%),and the stability(36124.2±1488.13,RSD was 4.12%)of the methodology were within the scope of requirements.2.The pharmacokinetic parameters of control group were AUC 1286.31(ug·mL^-1·min^-1),V_d 378.68(mL·kg^-1r),K_e 0.0277(·min^-1),t_1/2β69.70(min), CL_s 1.22(mL·kg^-1·min^-1);The pharmacokinetic parameters of experimental group before liver transplantation and after liver transplantation were AUC 2317.88 vs 1974.70(ug·mL^-1·min^-1),V_d 308.89 vs 323.74(mL·kg^-1),K_e 0.0374 vs 0.0291 (·min^-1),t_1/2β49.23 vs 25.38(min),CL_s 0.79 vs 0.78(mL·kg^-1·min^-1).Conclusion:1.The detection method was simple,stable,sensitive,which could be applied in the clinical pharmacokinetic study.2.There was a higher plasma level in patients with abnormal liver function after administration of vecuronium.The drug was eliminated slower and had a longer dosing interval.3.The elimination of vecuronium in patients before liver transplantation was slower so that it became more effective and had a longer pariod of maintenance.After the donor liver was transplanted into the patient,the drug was elimited faster.