基于NONMEN法建立万古霉素新生儿群体药动学模型

目的:建立新生儿万古霉素群体药动学模型,为临床个体化给药方案提供参考。方法:回顾性收集80例静脉使用万古霉素新生儿的170个稳态血药浓度数据及临床资料,运用非线性混合效应模型(NONMEM),建立新生儿万古霉素群体药动学(PPK)模型;考察各项协变量对药动学参数的影响,对最终模型进行拟合优度、自举法(Bootstrap)及正态预测分布误差法(NPDE)验证。利用蒙特卡洛法评估患儿在不同给药方案下的血药浓度范围。结果:一室模型能较好地拟合万古霉素体内过程,清除率(CL)和表观分布容积(V)的群体典型值分别为0.297L·h-1和2.230L,表观分布容积对CL有显著影响。拟合优度、Bootstrap和NPDE表明最终模型稳定、预测结果可靠。建立不同体质量范围新生儿万古霉素初始剂量推荐表。结论:本研究建立的新生儿万古霉素PPK模型稳定可靠,可为优化新生儿给药方案提供依据。     

万古霉素的群体药动学研究

目的研究万古霉素在革兰氏阳性菌感染患者中的群体药动学(PPK),指导临床合理用药。方法通过监测103个被诊断为革兰氏阳性菌感染患者的血清浓度,同时考虑患者的年龄、性别、身高及合并用药,以非线性混合效应模型(NONMEM)程序,按照线性二房室模型,建立并验证万古霉素PPK模型,根据患者的PPK模型参数制定个体化给药方案。结果最终模型中,万古霉素的清除率CL(L/h)与肌酐清除率CLCr(mL.min-1)呈线性关系:CL=0.044×CLCr;同时中央室的表观分布容积V1(L)与年龄呈线性相关:V1=0.542×Age;在验证组中,最终模型用于预测万古霉素的血药浓度,所建立的最终模型经验证具有良好稳定性和预测效能。结论肾功能和年龄对去甲万古霉索药动学参数有显著影响;根据上述研究结果可以给相似身体状况的患者制定万古霉素的个体化给药方案。     

大剂量甲氨蝶呤在急性淋巴细胞白血病患儿中的群体药动学

目的:研究大剂量甲氨蝶呤(HDMTX)在儿童急性淋巴细胞白血病(ALL)患者中的群体药动学(PPK)特征。方法:96例患儿接受HDMTX(3g·m-2)静脉滴注24h,收集24~68h左右稀疏血药浓度数据376个,采用荧光偏振免疫法(FPIA)测定MTX血药浓度。用NONMEM软件进行模型拟合和PPK参数的估算,并定量分析患儿年龄、性别、体质量、体表面积、种族、水化量、碱化量等固定效应对甲氨蝶呤PPK参数的影响,得到最终回归模型。结果:PPK模型为:中央室清除率(CL1)=5.04×(1-0.356×GEND)×BSA0.777 (OH1/100)0.514(L·h-1),中央室表观分布容积(V1)=16.1(L),外周室清除率(CL2)=0.203×(AGE/10)1.56(L·h-1),外周室表观分布容积(V2)=7.05×(AGE/10)1.76(L),CL1、V1、CL2、V2的群体标准值(个体间RSD%)分别为5.04L·h-1(49.6%),16.1L(29.3%),0.203L·h-1(337.6%),7.05L(107.7%),其中性别、体表面积及给药前碱化量对CL1的影响具有统计学意义,年龄对CL2及V2的影响具有统计学意义(P<0.01)。结论:本实验模型拟合情况较好,可为临床制定个体化给药方案、减少药物不良反应提供重要依据。     

万古霉素在新生儿和小婴儿患者中的群体药动学研究

目的建立万古霉素在新生儿和小婴儿患者的群体药动学(PPK)模型,为临床个体化用药提供参考。方法收集85例新生儿科患者静脉注射使用万古霉素后的血药浓度数据和临床资料。将患者分为两组,模型组(n=71)采用Phoenix~NLME~(TM)1.3软件进行PPK分析,建立一房室药动学模型(个体间变异采用指数模型,个体内变异采用混合误差模型),考察各协变量对参数V和CL的影响。用拟合优度、自举法对最终模型的性能进行内部验证。采用验证组(n=14)患者的血药浓度,计算平均预测误差(MPE)、平均绝对预测误差(MAE)、平均预测误差均方(MSPE)对最终模型进行外部验证。结果 PPK最终模型为V(L)=3.167,CL(L·h~(-1))=0.413×(WT/3.32)~(0.747)×(PNA/25)~(0.402)×e~(ηCL),体重(WT)和产后日龄(PNA)对CL有影响。拟合优度、自举验证的结果表明最终模型稳定、预测结果可靠。外部验证最终模型计算MPE、MAE和MSPE值分别为(-0.843±1.347)、(1.462±1.175)和(2.432±4.293)mg·L~(-1)。血药浓度实测值和最终模型的个体预测值的决定系数R=0.955,外部验证说明最终模型预测准确度较好。结论本研究建立的万古霉素新生儿和小婴儿患者的PPK模型预测能力和稳定性良好,可为其个体化给药方案的制订提供参考。     

Bayesian反馈法估算静脉输注伏立康唑的群体药动学参数

目的用Bayesian反馈法估算临床患者静脉输注伏立康唑的群体药动学(PPK)参数。方法收集静脉输注给药不同时间后的血样,采用HPLC法测定伏立康唑血药浓度,用Bayesian反馈法估算PPK参数。结果以二室模型拟合伏立康唑的药动学过程,得PPK参数为Vss为(46.58±19.35)L,CL为(4.76±2.64)L/h,k10为(0.187±0.006)h-1k,12为(4.97±0.02)h-1,k21为(0.895±0.308)h-1。结论此PPK模型能够较准确地描述伏立康唑在临床患者静脉输注的药动学特征,其预测能力尚待进一步评估。     

银屑病患者甲氨蝶呤的群体药动学研究

目的:研究银屑病患者甲氨蝶呤(MTX)的群体药动学特征,为临床调整个体化用药提供新途径。方法:收集皮肤科50例银屑病患者单剂量静脉滴注MTX后稀疏血药浓度数据137个,采用荧光偏振免疫法(FPIA)测定,应用非线性混合效应模型(NONMEM)程序一步法估算MTX的群体药动学参数,并定量分析患者年龄、性别、体质量、肌酐清除率、尿素氮等因素对MTX药动学参数的影响。结果:按静脉滴注二房室线性开放模型估算的群体药动学参数中央室清除率(CL)、中央室表观分布容积(Vc)、外周室表观分布容积(Vp)及外周室清除率(Q)分别为10.4L·h-1、11.7L、6.61L及2.8L·h-1,其个体间变异ωCL、ωVc、ωVp、ωQ分别为16.8%、2.8%、11.7%及287.9%。且最终回归模型的MTX浓度估算值与实测值具有一致性。效应中尿素氮对Vp的影响具有显著意义(P>0.05),其协变量参数为(尿素氮/4)-0.845。结论:NONMEM法以二室模型群体参数估算的血药浓度值与实测值有良好相关性,此研究结果有助于MTX的临床合理应用。     

中国健康受试者口服法罗培南钠片的群体药代动力学

目的:建立中国健康受试者口服法罗培南钠片的群体药代动力学(PPK)模型,研究法罗培南在中国健康人体内的药动学特点,评价法罗培南药动学的影响因素。方法:基于两个临床研究中心的健康受试者的临床研究资料,利用Phoenix NLME软件建立法罗培南的群体药代动力学模型,并用VPC验证法和自举法进行验证。结果:法罗培南在健康志愿者体内的药代动力学符合有滞后时间的一级消除动力学一房室模型,个体间变异符合指数模型。法罗培南清除率(CL/F)和分布容积(V/F)的群体典型值分别为650.68mL·h-1·kg-1和594.24mL/kg。结论:饮食、性别对法罗培南的群体药代动力学参数有显著影响。所建立的PPK模型可以较好地估算服用法罗培南的的个体及群体药动学参数,为指导临床合理用药提供药动学参考。     

左旋多巴中国人群药动学模型的建立

目的:建立中国人群左旋多巴/苄丝肼复合制剂中左旋多巴的群体药动学模型。方法:前瞻性收集服用多巴丝肼片的帕金森病(PD)门诊患者稳态谷浓度97例102个血样和健康志愿者13例153个密集血样,高效液相色谱-电化学(HPLC-ECD)法测定左旋多巴(LD)血药浓度。应用NONMEM软件进行群体药动学数据分析,Bootstrap重复抽样用于模型的内部验证。另收集20例PD患者22个血样点作为验证组进行模型外部验证,计算最简模型和最终模型对验证组的平均预测误差(MPE)和平均绝对误差(MAE)对模型进行外部验证。结果:数据采用一房室模型拟合,年龄(AGE)对LD清除率有显著影响,性别(SEX)、体质量(WT)、给药剂量(TAMT)、合并用药不影响LD的药动学参数。LD的基础模型为:CL(CL/F)(L.h-1)=18.2×EXP[ETA(1)],V(V/F)(L)=48.4,ka(h-1)=2.13×EXP[ETA(2)];最终模型为:CL(CL/F)(L.h-1)=17.9×(55/AGE)0.59×(EXP[ETA(1)],V(V/F)(L)=47.5,ka(h-1)=2.14×EXP[ETA(2)]。CL、V、ka的群体典型值分别为17.9 L.h-1、47.5 L、2.14 h-1。Bootstrap重复抽样显示所建立的最终模型稳定、可靠,最终模型对验证组的MPE和MAE较最简模型有显著改善,显示模型有效,且有一定代表性。结论:根据患者的生理用药资料,结合上述模型,可估算个体药动学参数,为临床个体化给药提供参考。     

非线性混合效应模型法估算癫痫患者卡马西平的群体药动学参数

目的:建立癫痫患者卡马西平(CBZ)的群体药动学(PPK)模型。方法:采集我院服用CBZ的270例门诊癫痫患者的稳态血药浓度数据(共316个样本)以及患者相关资料数据。应用非线性混合效应模型(NONMEM)法估算癫痫患者CBZ的PPK参数值,建立PPK模型。并运用自举法(Bootstrap)验证模型的可靠性。结果:年龄(AGE)、每日服药剂量(DKG)、体质量(BW)均为CBZ清除率(CL)的影响因素。最终模型:当AGE≤14岁时,CL(L/h)=[2.55+0.013×(AGE-15)]×(DKG/0.011)0.443×(BW/40)0.392;AGE>14岁时,CL(L/h)=2.55×(DKG/0.011)0.443×(BW/40)0.392。表观分布容积(Vd)=85L。经Bootstrap法验证,本模型稳定、可靠。结论:用NONMEM软件成功建立我院癫痫患者服用CBZ的PPK模型。根据本院癫痫患者的PPK模型,结合患者DKG、BW和合并用药可估算其CL,优化临床个体化用药方案。     

成人慢性肾小球肾炎患者他克莫司群体药动学研究

目的:建立成人慢性肾小球肾炎患者他克莫司群体药动学(population pharmaco-kinetics,PPK)模型。方法:收集55例慢性肾小球肾炎患者的268个他克莫司血药浓度数据。采用非线性混合效应模型考察CYP3A5基因型、体质量、年龄、实验室指标、合并用药等对他克莫司药动学参数的影响,建立他克莫司PPK模型,并通过拟合优度诊断、Bootstrap自举法及正态预测分布误差法对模型进行验证。结果:他克莫司表观清除率及表观分布容积的群体典型值分别为13.8L·h-1和733L,CYP3A5基因型和合并用药五酯胶囊对他克莫司清除率具有显著影响。经验证他克莫司PPK模型稳定有效。结论:首次建立成人慢性肾小球肾炎患者他克莫司PPK模型,可为慢性肾小球肾炎患者的他克莫司个体化给药提供参考。     

High dose methotrexate population pharmacokinetics and Bayesian estimation in patients with lymphoid malignancy

The purpose of present study was to develop a population pharmacokinetic model of high dose methotrexate (HD‐MTX) infusion in patients with lymphoid malignancy, to investigate the biological and clinical covariates related to the drug distribution and elimination. It is also the purpose to propose a limited sampling strategy (LSS) for the estimation of the time above the threshold (0.2 µmol·L^?1). A total 82 patients with lymphoid malignancy were involved in the study. A pharmacokinetic model was developed using nonlinear mixed‐effect model. The influence of demographic characteristics, biological factors, and concurrent administration were investigated. The final predictive performance was validated by bootstrap and cross‐validation. Bayesian estimation was evaluated. The pharmacokinetics of HD‐MTX was described by a two‐compartment model. The pharmacokinetic parameters and the inter‐individual variability were as follows: the clearance CL, 7.45 L·h^?1 (inter‐individual variability 50.6%), the volume of the central and peripheral compartment V₁, 25.9 L (22.5%), V₂, 9.23 L (97.8%), respectively, and the intercompartmental clearance Q, 0.333 L·h^?1 (70.4%). The influence of serum creatinine on CL and weight on V₁ was retained in the final model. The protocol involved one sampling time at 44 h after the start of the infusion, allowing one to predict the time at which the MTX concentration reached the expected threshold (0.2 µmol·L^?1). Serum creatinine and weight showed significant influence on methotrexate CL and V₁, respectively. Furthermore, a Bayesian estimation based on the covariates and 44 h sample was developed, allowing prediction of the individual methotrexate pharmacokinetic parameters and the time to 0.2 µmol·L^?1. Copyright © 2009 John Wiley & Sons, Ltd.     

何首乌有效成分二苯乙烯苷的药代动力学研究

目的建立小鼠和兔血浆中二苯乙烯苷浓度的HPLC测定方法,研究何首乌中二苯乙烯苷在小鼠和兔体内的药代动力学行为。方法用Diamonsil^TM C₁₈色谱柱(250 mm×4.6 mm,5 μm),以乙腈-甲醇-1%甲酸(15∶18∶67)为流动相,流速1.0 mL·min^-1,检测波长320 nm。结果线性范围为0.41～42.0 μg·mL^-1(γ=0.9999),最低检测浓度为0.051 μg·mL^-1。高、中、低3种不同浓度的平均回收率分别为97.98%,101.7%和104.5%,日内精密度RSD分别为8.7%,2.9%和5.5%。小鼠和兔iv二苯乙烯苷后药代动力学行为均符合二室模型,药代动力学参数分别为:T_1/2α=1.9,2.7 min;T_1/2β=8.3,13.5 min;K₂₁=6.6,4.2 h^-1;K₁₂=3.8,3.0 h^-1;K₁₀=16.0,11.2 h^-1;V_c=0.090,0.198 L·kg^-1;AUC=6.918,4.530 mg·h·L^-1;CL=1.445,2.208 L·h^-1·kg^-1。小鼠ig给药后二苯乙烯苷在胃肠道内的吸收不规则,且血药浓度很低,药代动力学行为不符合房室模型。结论建立了二苯乙烯苷血药浓度的HPLC测定方法,阐明了二苯乙烯苷的药代动力学特征。方法的专属性高,操作简便,结果准确。     

Population pharmacokinetic analysis of vancomycin in neonates. A new proposal of initial dosage guideline

AIM

To determine the population pharmacokinetic parameters of vancomycin in neonatal patients with a wide range of gestational age and birth weight, and subsequently to design an initial dosing schedule for vancomycin in neonates.

METHODS

Using nonlinear mixed-effects modelling (NONMEM VI), the pharmacokinetics of vancomycin were investigated in 70 neonates with postmenstrual age and body weight ranging 25.1–48.1 weeks and 0.7–3.7 kg, respectively. A one-compartment linear disposition model with zero order input and first-order elimination was used to describe the data. Nine demographic characteristics and 21 co-administered drugs were evaluated as covariates of clearance (CL) and distribution volume (V_d) of vancomycin.

RESULTS

Weight-normalized clearance of vancomycin was influenced by postmenstrual age (PMA) and co-administration of amoxicillin-clavulanic acid. Weight-normalized volume of distribution was influenced by co-administration of spironolactone. CL and V_d of the typical individual in this study population (PMA = 34.6 weeks, weight = 1.7 kg) were estimated to be 0.066 l h⁻¹ kg⁻¹ (95% CI 0.059, 0.073 l h⁻¹ kg⁻¹) and 0.572 l kg⁻¹ (95% CI 0.505, 0.639 l kg⁻¹), respectively. This model was used to predict a priori serum vancomycin concentrations in a validation group (n= 41), which were compared with observed concentrations to determine the predictive performance of the model. The 95% confidence interval of mean prediction error included zero for both peak and trough vancomycin concentrations.

CONCLUSIONS

Postmenstrual age, co-administration of amoxicillin-clavulanic acid and spironolactone have a significant effect on the weight-normalized CL and V_d. An initial dosage guideline for vancomycin is proposed for preterm and full-term neonates, whereas the population pharmacokinetic model can be used for dosage individualization of vancomycin.     

安定在家兔体内的肠胃循环药代动力学分析

6只家兔iv安定5 mg·kg^-1后,浓度—时间数据呈现双峰形。本文提出肠胃循环动力学模型,用于分析实测数据,得到了一般动力学参数:T_1/2(α)=0.21±=0.15 h,T_1/2(β)=2.2+0.6 h,K_e=1.5±0.6 h^-1,K₁₂=2.0±1.0 h^-1,K₂₁=1.0±0.4 h^-1,V₁=3.1±1.6 L·kg^-1,AUC=1.7±0.5μg·h^-1·ml^-1。此外,还求得有关肠胃循环的参数,即:重吸收滞后时间T′=0.25±0.24h,重吸收速率常数K_A=3.5±1.4 h^-1,重吸收率R_A=24±7%。     

基于群体药动学原理对1例新生儿败血症合并脑膜炎的药学监护

目的 为临床制定万古霉素个体化给药方案提供参考。方法 临床药师运用万古霉素群体药动学模型对1例新生儿败血症合并脑膜炎病例开展个体化给药方案调整和实施药学监护。结果 在基于治疗药物的监测和万古霉素群体药动学模型制定的万古霉素静脉注射联合脑室内注射的给药方案下,患儿感染得到有效控制,无不良反应发生。结论 临床药师应用群体药动学模型优化万古霉素抗感染治疗方案,协助临床医师制定个体化给药方案。     

HPLC-MS/MS法测定血浆中十肽化合物LXT-101及Beagle犬药代动力学研究

建立HPLC-MS/MS法测定血浆中十肽化合物(LXT-101)的浓度，并应用于Beagle犬的药代动力学研究。血浆样品采用乙腈直接沉淀蛋白的方法，内标(IS)选用¹²⁷I-LXT-101，采用ESI-MS/MS二极质谱，选择反应监测(SRM)方式进行检测。LXT-101的线性范围为0.5～500.0 ng·mL^-1(r²>0.993 0)，绝对回收率为85.2%～90.7%，日内、日间精密度(RSD%)均小于10.9%，准确度(RE)在±1.8%之内。血浆中的最低检测限(LOQ)为0.5 ng·mL^-1。该法操作简便、快速、灵敏度高。可检测出低剂量肌注(im)给药后犬体内的血药浓度，适于临床前药代动力学研究。     

Prediction of clinical pharmacokinetic parameters of linezolid using animal data by allometric scaling: applicability for the development of novel oxazolidinones

1.?Allometric scaling has previously been used as an effective tool for the prediction of human pharmacokinetic data. The pharmacokinetic data for linezolid, a novel oxazolidinone to treat Gram-positive pathogens, in mice, rats and dogs were subjected to simple allometric scaling. Generated allometric equations for parameters such as clearance (CL), volume of distribution (V_ss) and elimination rate constant (K₁₀) were used to predict human pharmacokinetic parameters including elimination half-lives. In addition, the human plasma concentration–time curve was simulated using a one-compartmental model.

2.?Application of simple allometry (Y?=?aW^b) for animal parameters such as CL, V_ss, and K₁₀ showed excellent allometric fit (r?≥?0.98). The allometric equations for CL, V_ss, and K₁₀ were??0.5465W^0.6595,??0.1369W^0.9246, and??0.4117W^–0.3139, respectively. The confidence in predictability of CL and V_ss parameters was particularly high since the allometric exponents of CL and V_ss almost approached the suggested values of 0.75 and 1.00, respectively.

3.?Animal pharmacokinetic parameters generated in the present authors’?laboratories for linezolid were in close agreement with reported literature values. The predicted human values for CL (4.68?l?h^?1), V_ss (37.07 litres), and K₁₀ (0.10?h^?1) were within the range observed for linezolid in the literature (CL?=?4?10.5 l?h^?1; V_ss?=?21???53 litres; K₁₀?=?0.09???0.3?h^?1). The human half-life (t_1/2) predicted using allometry (6.9?h) was similar to reported values in humans of 5?h. In summary, the retrospective analysis for linezolid suggests that allometric scaling can be used as a prospective tool for predicting human pharmacokinetic parameters of novel oxazolidinones.     

PHARMACOKINETICS AND HAEMATOLOGICAL PARAMETERS OF RECOMBINANT HUMAN ERYTHROPOIETIN AFTER SUBCUTANEOUS ADMINISTRATIONS IN HORSES

The pharmacokinetics of recombinant human Epo (rHuEpo) were investigated after subcutaneous administration to horses. Four horses received a single 30 IU kg⁻¹ dose of rHuEpo. One horse received three repeated doses of 120 IU kg⁻¹ at 48 h intervals. Plasma erythropoietin (Epo) was measured by radioimmunoassay. In both cases pharmacokinetic parameters were evaluated using a one-compartment open model and first-order input and output rates. The mean values (±SD) for elimination half-life, CL/F, and V_d/F after a single dose were 12·9±3·34 h, 11·8±4·96 L h⁻¹, and 233±126 L, respectively. After repeated doses, elimination half-life, CL/F, and V_dss/F were 11·3 h, 8·94 L h⁻¹, and 145·6 L, respectively. No significant differences were observed between the haematological parameters after a single 30 IU kg⁻¹ administration compared to baseline values. Multiple and high doses of rHuEpo modified red blood cells, haemoglobin, and hematocrit. According to our results, plasma Epo assay can help, during an antidoping control procedure, to support a positive result only up to 72 h after the last rHuEpo     

Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy

Aim:

To establish a population pharmacokinetics (PPK) model of levetiracetam in Chinese children with epilepsy.

Methods:

A total of 418 samples from 361 epileptic children in Peking University First Hospital were analyzed. These patients were divided into two groups: the PPK model group (n=311) and the PPK validation group (n=50). Levetiracetam concentrations were determined by HPLC. The PPK model of levetiracetam was established using NONMEM, according to a one-compartment model with first-order absorption and elimination. To validate the model, the mean prediction error (MPE), mean squared prediction error (MSPE), root mean-squared prediction error (RMSPE), weight residues (WRES), and the 95% confidence intervals (95% CI) were calculated.

Results:

A regression equation of the basic model of levetiracetam was obtained, with clearance (CL/F)=0.988 L/h, volume of distribution (V/F)=12.3 L, and K_a=1.95 h⁻¹. The final model was as follows: K_a=1.56 h⁻¹, V/F=12.1 (L), CL/F=1.04×(WEIG/25)^0.583 (L/h). For the basic model, the MPE, MSPE, RMSPE, WRES, and the 95%CI were 9.834 (−0.587–197.720), 50.919 (0.012–1286.429), 1.680 (0.021–34.184), and 0.0621 (−1.100–1.980). For the final model, the MPE, MSPE, RMSPE, WRES, and the 95% CI were 0.199 (−0.369–0.563), 0.002082 (0.00001–0.01054), 0.0293 (0.001−0.110), and 0.153 (−0.030–1.950).

Conclusion:

A one-compartment model with first-order absorption adequately described the levetiracetam concentrations. Body weight was identified as a significant covariate for levetiracetam clearance in this study. This model will be valuable to facilitate individualized dosage regimens.     

咪达唑仑片在中国维吾尔族和汉族健康人体的药动学比较

目的研究健康维吾尔族和汉族志愿者单剂量口服咪达唑仑片的药动学。方法维吾尔族、汉族健康志愿者各10名,男、女各半,单剂量口服15 mg咪达唑仑片后,用HPLC法测定咪达唑仑的血浆浓度,运用DAS 2.0程序以非室模型拟合药动学参数,并对药动学参数进行独立样本t检验和非参数Mann-Whitney U test检验,以判断药动学是否存在显著性的民族差异。结果单剂量口服15 mg咪达唑仑片后,维吾尔族志愿者的主要药动学参数分别为:ρmax(124.8±50.0)μg.L-1,tmax(0.8±0.5)h,t1/2z(1.9±0.7)h,MRT0-12 h(2.8±0.8)h,CL/F(0.9±0.4)L.h-1.kg-1,Vz/F(2.3±0.7)L.kg-1和AUC0-12 h(343.2±150.9)μg.h.L-1。汉族健康受试者的主要药动学参数分别为:ρmax(103.1±26.4)μg.L-1,tmax(1.5±0.7)h,t1/2z(3.0±0.8)h,MRT0-12 h(3.6±0.4)h,CL/F(0.7±0.2)L.h-.1kg-1,Vz/F(2.7±0.8)L.kg-1和AUC0-12 h(368.8±103.4)μg.h.L-1。经检验,维吾尔族的tmax、t1/2z和MRT0-12 h比汉族的短,差异有显著性统计学意义,其余参数的民族差异无显著性统计学意义。两个民族的部分受试者的药-时曲线有双峰。结论单剂量口服咪达唑仑片后,汉族和维吾尔族健康志愿者的药动学存在较大的个体差异,且消除速率的民族差异有显著性统计学意义,临床应用时应注意个体化给药。