Pharmacokinetic Comparison Of Domestic Alfentanil In Elderly And Young Adults

Objectives To compare the pharmacokinetic characteristics of domestic alfentanil in elderly and young adults undergoing surgery,in order to provide clinical data for the application of alfentanil in China,and to provide scientific basis for rational clinical use of alfentanil.Methods A total of 60 patients with ASAⅠ-II grade who underwent total thyroidectomy under general anesthesia were selected,regardless of gender,including 30 elderly patients（65-79 years old）and 30 young adults（25-45 years old）with BMI<28kg/m².After the patients entered the operating room,the NIBP,HR,ECG,Sp O₂ and BIS were monitored.Intravenous infusion of sodium lactate ringer injection with indwelling needle in upper extremity.Puncturing the radial artery and catheterizing to detect arterial blood pressure.Midazolam 0.02-0.05mg/kg,etomidate 0.2-0.3mg/kg and cisacurvum 0.2-0.3mg/kg were intravenously injected through the upper limb vein,and alfentanil 50μg/kg was intravenously injected during induction.Tracheal intubation and mechanical ventilation were performed after 3-5 minutes.Sevoflurane 3%-4%and oxygen flow 1-2L/min was used in both groups intraoperatively.The monitoring value of BIS was controlled at 40-60 to maintain the appropriate depth of anesthesia.One-third of the induced dose of cisatracurium was given intravenously for half an hour until half an hour before the end of surgery.The anesthesia time,operation time and dosage of sevoflurane were recorded.Vital signs such as MAP,HR,Sp O₂ and BIS were recorded at 30 min before anesthesia induction（T₀）,induction time（T₁）,skin incision time（T₂）,end time of the operation（T₃）and 2h after the operation（T₄）.3ml blood was collected from radial artery before intravenous injection of alfentanil.The stopwatch time was counted immediately after injection,and 3ml blood was collected from radial artery again at 1,2,3,5,7,10,15,30,60,120,240 and 300 min after injection.The blood was centrifuged for 10 minutes（3000r/min）in a disposable heparinized vacuum blood collection vessel,and 1ml of plasma was extracted.The blood was placed in the tube and stored at-80℃until analysis.Plasma drug concentration was determined by LC-MS/MS method.The stock solution and standard solution were prepared and the standard curve was obtained.The quality control samples were prepared,the chromatographic and mass spectrometric conditions were determined,and the methodology was verified.After the determination of the method,the plasma drug concentration was determined.DAS 3.0software was used to analyze the results of pharmacokinetic parameters.SPSS 19.0 was used for statistical analysis,and P<0.05 was statistically significant.Results 1 There was a difference in age between the two groups（P<0.01）,and there was no statistical difference in other general situation data（P>0.05）.2 There was no significant difference in MAP,HR,Sp O₂ and BIS at all time points between the two groups.3 The pharmacokinetics of alfentanil in the elderly group and the young group were in accordance with the open two compartment model.The concentration of alfentanil in blood increased to the maximum immediately after administration and then decreased rapidly,in line with the first-order elimination kinetics.4 There was no difference inαand t_1/2αbetween the two groups（P>0.05）;βin the elderly group（0.0046±0.0011）min^-1 was smaller than that in the young adults group（0.0076±0.0016）min^-1,and the t_1/2βin the elderly group（145.333±48.915）min was longer than that in the young adults group（89±20.403）min（P<0.001）.Vc in the elderly group（0.251±0.036）L/kg was larger than that in the young group（0.159±0.065）L/kg（P<0.001）;Vd in the elderly group（0.813±0.177）L/kg was larger than that in the young group（0.616±0.270）L/kg（P<0.01）.CL in the elderly group（3.807±1.257）ml/kg/min was smaller than that in the young group（6.234±1.880）ml/kg/min.The elimination rate constants K₁₂and K₂₁ had no significant difference between the two groups（P>0.05）.However,K₁₀ in the elderly group（0.014±0.004）min^-1 was smaller than that in the young group（0.031±0.012）min^-1（P<0.001）.Conclusions 1 In this study,the pharmacokinetics of alfentanil in two groups are in line with the open two-compartment model,and the decreasing trend of drug concentration of the two groups is in line with the first-order elimination kinetics.2 There are significant differences inβ,t_1/2β,CL,K₁₀,Vc and Vd between the elderly group and the young group.Figure 14;Table 6;Reference 126...