Pharmacokinetics Of Domestic Alfentanil In Obese Patients

Objective Objective to determine the concentration of alfentanil in human plasma by liquid chromatography tandem mass spectrometry（LC-MS/MS）,calculate the pharmacokinetic parameters of alfentanil in obese patients and ordinary patients,and analyze its pharmacokinetic characteristics,so as to provide scientific basis for clinical application of alfentanil.Methods Sixty patients（33 males and 27 females）with ASA grade I or II were randomly selected for total thyroidectomy under general anesthesia.According to the evaluation of body mass index,they were divided into two groups:group O（obese group）30 cases（male 17 cases,female 13 cases）;group C（control group）30 cases（male 16 cases,female14 cases）.There was no history of alcohol drinking,obesity and drug-induced obesity,no previous opioid sensitivity,no use of opioid or cytochrome P450 responsive drugs,no history of opioid or narcotic drug abuse,no mental system,endocrine system,heart,brain,liver and kidney diseases,no fever.All patients had no preoperative medication,and the room temperature in the operating room was kept between 22℃and 24℃.Noninvasive blood pressure,heart rate,electrocardiogram and pulse oxygen saturation were monitored after admission.The right upper limb was opened for intravenous infusion of sodium lactate Ringer’s solution.The left radial artery was punctured and catheterized under local anesthesia.After 2 minutes,midazolam(0.02-0.05mg·kg^-1),etomidate(0.2-0.3mg·kg^-1)and cisatracurium(0.2-0.3mg·kg^-1)were given through the upper extremity vein.During induction,fentanyl(50μg·kg^-1)was injected intravenously.After 3 minutes of pure oxygen ventilation,endotracheal intubation and mechanical ventilation were performed.The respiratory parameters were set as follows:Tidal Volume 6-8ml·kg-1,respiratory rate 12-15 times/min,inspiratory/expiratory ratio 1:2,Pet CO2 35-45mm Hg,BIS 40-60,and appropriate depth of anesthesia.Anesthesia was maintained by inhalation with sevoflurane concentration of 3%-4%and oxygen flow of 1-2 L·min^-1.1/3 of cisatracurium was injected intravenously for 30minutes until 30minutes before the end of operation.Anesthesia time,operation time and sevoflurane dosage were recorded.Vital signs such as mean arterial pressure,heart rate,Sp O2 and BIS value were recorded at 30 minutes before induction（T₀）,induction time（T₁）,skin incision time（T₂）,operation end time（T₃）and 2 hours after operation（T₄）.At the end of intravenous injection of alfentanil,the stopwatch was used to count the time,and 3 ml of blood was collected from the left radial artery before injection and 1,2,3,5,7,10,15,30,60,120,240,and 300 min after injection.After centrifugation for 10min(3000r·min^-1),1ml of plasma was precisely extracted,put into a test tube,and stored in a refrigerator at-80℃.The standard solution and quality control samples were prepared Standard curve.LC-MS/MS method was used to determine the plasma concentration.The pharmacokinetic parameters were analyzed with DAS 3.0 software and SPSS 19.0 software.Results Except for body weight and body mass index,there were no significant differences between the two groups.At the end of the operation,the mean arterial pressure of the obese group was（88±11）mm Hg,which was significantly lower than that of the control group（92±6）mm Hg.The pharmacokinetics of alfentanil in obesity group and control group were consistent with the open two compartment model.After administration,the plasma concentration of alfentanil reached the peak rapidly and then decreased rapidly,which conformed to the first-order elimination kinetics.There was no significant difference inα,T_1/2α,Vd and Vc between the two groups.β(0.006257±0.001242min^-1)in the obese group was smaller than that in the control group(0.00762±0.001679min^-1),and T_1/2β（115.567±26.094min）in the obese group was longer than that in the control group（89±20.402min）.The CL of obesity group(4.164±1.045ml·kg^-1·min^-1)was lower than that of control group(6.234±1.879ml·kg^-1·min^-1).In the elimination rate constants K₁₂ and K₂₁,the values of K₁₂ and K₂₁ were not significantly different between the obese group and the control group,while K₁₀(0.0246±0.0088 min^-1)in the obese group was smaller than that in the control group(0.031±0.011 min^-1).In control group and obesity group,the clearance rate of central ventricle to peripheral ventricle was higher than that of peripheral ventricle to central ventricle.Conclusion To observe the pharmacokinetics of alfentanil in obese and non obese patients undergoing elective total thyroidectomy under general anesthesia.1 In this study,the pharmacokinetics of alfentanil in the two groups were consistent with the open two compartment model,which can be expressed by exponential function.2 The pharmacokinetic parameters ofβ,T_1/2β,CL and K₁₀in obese patients were significantly different from those in control group.The T_1/2βof obese patients was longer than that of non obese patients,and the CL was lower than that of non obese patients.Therefore,more attention should be paid to the respiratory and circulatory conditions of obese patients after operation,and respiratory support should be given when necessary.Figure13;Table8;Reference 153...