临床麻醉学杂志
臨床痳醉學雜誌
림상마취학잡지
THE JOURNAL OF CLINICAL ANESTHESIOLOGY
2014年
12期
1156-1160
,共5页
王强%鲍方%刘礼军%桂勤芳%马正良
王彊%鮑方%劉禮軍%桂勤芳%馬正良
왕강%포방%류례군%계근방%마정량
瑞芬太尼%群体药代动力学%非线性混合效应模型
瑞芬太尼%群體藥代動力學%非線性混閤效應模型
서분태니%군체약대동역학%비선성혼합효응모형
Remifentanil%Population pharmacokinetics%Nonlinear mixed effect model (NONMEM)
目的:探讨影响成人患者瑞芬太尼药代动力学的可能因素,并初步建立其群体药代动力学模型。方法全麻择期腹部大手术患者11例,年龄25~86岁,随机确定瑞芬太尼输注速度为0.3μg·kg-1·min-1(R3组)或0.6μg·kg-1·min-1(R6组)。按预设时间采集动脉血样本分析血药浓度,非线性混合效应模型(NONMEM)建立群体药代动力学模型。结果瑞芬太尼药代动力学适合用三室模型描述,初期分析表明年龄、身高和 BMI 不影响药代动力学参数,而瘦体重(LBM)、体表面积(BSA)和性别有明显影响(P<0.01);进一步以后退法验证仅体重显著影响瑞芬太尼的系统清除率(CL)和中央室容积(V)。60 kg 患者瑞芬太尼药代动力学参数典型值为 V1=7.61 L,V2=4.81 L,V3=4.34 L,CL1=2.74 L/min,CL2=0.738 L/min,CL3=0.0905 L/min。结论瑞芬太尼的药代动力学特点与其经血液和组织酯酶迅速水解的特点一致。在研究涉及的协变量范围内,系统清除率和中央室容积随体重增加而增加,提示较大体重的患者需要较大剂量的初始输注速度和维持剂量以获得稳定的血浆浓度和临床效应。
目的:探討影響成人患者瑞芬太尼藥代動力學的可能因素,併初步建立其群體藥代動力學模型。方法全痳擇期腹部大手術患者11例,年齡25~86歲,隨機確定瑞芬太尼輸註速度為0.3μg·kg-1·min-1(R3組)或0.6μg·kg-1·min-1(R6組)。按預設時間採集動脈血樣本分析血藥濃度,非線性混閤效應模型(NONMEM)建立群體藥代動力學模型。結果瑞芬太尼藥代動力學適閤用三室模型描述,初期分析錶明年齡、身高和 BMI 不影響藥代動力學參數,而瘦體重(LBM)、體錶麵積(BSA)和性彆有明顯影響(P<0.01);進一步以後退法驗證僅體重顯著影響瑞芬太尼的繫統清除率(CL)和中央室容積(V)。60 kg 患者瑞芬太尼藥代動力學參數典型值為 V1=7.61 L,V2=4.81 L,V3=4.34 L,CL1=2.74 L/min,CL2=0.738 L/min,CL3=0.0905 L/min。結論瑞芬太尼的藥代動力學特點與其經血液和組織酯酶迅速水解的特點一緻。在研究涉及的協變量範圍內,繫統清除率和中央室容積隨體重增加而增加,提示較大體重的患者需要較大劑量的初始輸註速度和維持劑量以穫得穩定的血漿濃度和臨床效應。
목적:탐토영향성인환자서분태니약대동역학적가능인소,병초보건립기군체약대동역학모형。방법전마택기복부대수술환자11례,년령25~86세,수궤학정서분태니수주속도위0.3μg·kg-1·min-1(R3조)혹0.6μg·kg-1·min-1(R6조)。안예설시간채집동맥혈양본분석혈약농도,비선성혼합효응모형(NONMEM)건립군체약대동역학모형。결과서분태니약대동역학괄합용삼실모형묘술,초기분석표명년령、신고화 BMI 불영향약대동역학삼수,이수체중(LBM)、체표면적(BSA)화성별유명현영향(P<0.01);진일보이후퇴법험증부체중현저영향서분태니적계통청제솔(CL)화중앙실용적(V)。60 kg 환자서분태니약대동역학삼수전형치위 V1=7.61 L,V2=4.81 L,V3=4.34 L,CL1=2.74 L/min,CL2=0.738 L/min,CL3=0.0905 L/min。결론서분태니적약대동역학특점여기경혈액화조직지매신속수해적특점일치。재연구섭급적협변량범위내,계통청제솔화중앙실용적수체중증가이증가,제시교대체중적환자수요교대제량적초시수주속도화유지제량이획득은정적혈장농도화림상효응。
Objective The aim of this study was to explore possible pharmacokinetic factors and develop a population pharmacokinetic model for remifentanil in adult patients.Methods Eleven healthy patients,undergoing elective major abdominal surgery,aged 25 to 86 years,received random-ly remifentanil 0.3μg·kg-1 ·min-1 (group R3),or 0.6μg·kg-1 ·min-1 (group R6).Frequent ar-terial blood samples were drawn according to predetermined time and assayed for remifentanil concen-tration.Nonlinear mixed-effects modeling (NONMEM)was used to evaluate the time courses of the measured concentrations.The covariates include age,bodyweight (WT),gender,lean body mass (LBM),body mass index (BMI)and body surface area (BSA).Results The pharmacokinetic data of remifentanil were well described using a three-compartment linear model with first-order elimination from the central compartment.Forward analysis showed that age,height and body mass index (BMI) does not affect the pharmacokinetic parameters,which are contrast with body weight,lean body mass (LBM),body surface area (BSA)and gender;further analysis demonstrated only a significant effect of body weight on remifentanil systemic clearance (CL)and volume of the central compartment (V). For typical 60 years patients,PK parameters were:V1 =7.64 L,V2 =4.81 L,V3 =4.34 L,CL1 =2.74 L/min,CL2 = 0.738 L/min,CL3 = 0.0905 L/min.Conclusion The pharmacokinetics of remifentanil is consistent with its rapid elimination by blood and tissue esterase in Chinese patients. The systemic clearance and volume of distribution of central compartment increases with body weight in the population and the range of covariates studied,which suggests that a patient with greater body weight needs a greater initial dose and maintenance infusion rate higher to obtain a stable plasma con-centrations and clinical effects.