国产加替沙星片剂在中国男性健康受试者的临床药代动力学及生物等效性研究

目的 :研究国产加替沙星片剂在健康男性志愿者中的药代动力学及生物等效性和安全性。方法 :2 4名男性受试者按双交叉随机开放试验设计 ,每名受试者单次空腹口服国产或进口片剂 4 0 0mg ,采用高效液相色谱法测定其血药浓度和尿药浓度。结果 :受试者单剂空腹口服国产和进口加替沙星片剂后体内过程均符合血管外二室模型 ,平均血药高峰浓度 (Cmax)分别为 4 .4 5± 1.0 4和 4 .0 5±0 .85mg·L-1,平均达峰中位时间 (Tmax)分别为 0 .75(0 .5 ,3)h和 0 .75 (0 .5 ,2 .5 )h ,平均消除半衰期(T1 2 β)为 6 .97± 1.0 8和 7.19± 0 .91h ,平均药时曲线下面积AUC0～∞ 分别为 31.99± 3.80和 32 .11±3.37mg·h-1·L-1。 4 8h内平均累积尿排出率分别为 (79.4 7± 6 .0 0 ) %和 (79.5 9± 5 .89) %。与进口片剂相比 ,两制剂间的主要药代动力学参数相近 ,其差异经统计学处理均无显著性 ,其相对生物利用度为(99.74± 7.4 2 ) %。结论 :受试者单剂空腹口服国产加替沙星片剂 4 0 0mg后体内过程符合血管外二室模型 ,其有效血药浓度维持时间长 ,原型药物在尿中排出率高。与进口片剂具生物等效性。     

拉米夫定片剂在中国健康男女受试者体内的药代动力学研究

观察拉米夫定在中国健康男女受试者体内的药代动力学特点，本研究采用高效液相色谱分析法，对国人单剂量多次口服拉米夫定的药代动力学过程进行了研究。结果显示，受试者在１次口服１００ｍｇ拉米夫定后，拉米夫定的血药浓度在０．８９ｈ左右达到高峰，其后快速下降，消除相半衰期；第７次口服１００ｍｇ拉米夫定后，拉米夫定的血药浓度在０．８２ｈ左右达到高峰，其后亦快速下降，研究结果未显示该药有体内蓄积现象，并且服药第１ｄ     

健康志愿者口服对乙酰氨基酚的时间药代动力学

目的 研究不同时辰服药对乙酰氨基酚药动学的影响。方法 不同时辰服药，测定其唾液浓度，计算药动学参数。结果 与20：00组相比，8：00时服药，药物吸收较快，达峰时间较短．但吸收程度较差，清除较快，在体内的平均驻留时间较短。结论 早、晚服用对乙酰氨基酚，其代谢存在时辰差异。     

萘丁美酮片药物动力学研究

萘丁美酮(nabumetone)是非甾体类消炎解热镇痛药。它是一种前体药物,在体内转化为6-甲氧基-2-萘乙酸(6-MNA)后才显示出较强的药理作用。本文作者采用反相高效液相色谱法测定6名正常健康志愿者口服单剂量100mg萘丁美酮片后的药物动力学。现报道如下。     

口服普萘洛尔在健康中国人药物动力学的性别差异

确定口服普萘洛尔的体内分布与代谢是否在健康中国人中存在性别二态性。１２名健康志愿者（６男，６女）口服单剂量Ｐｒｏ８０ｍｇ，其血浆Ｐｒｏ浓度用ＨＰＬＣ荧光法检测，药物动力学参数用ＭＣＰＫＰ软件计算。女性的ＡＵＣ和Ｃｍａｘ分别比男性高７４％和９９％，相反，Ｃｌｏ和Ｖｄ却分别比男性低１０９％和１２０％。     

医学研究中受试者权益保护的伦理审查

本研究回顾了医学科研伦理中受试者保护规范的发展历程，介绍了医学伦理审查的基本目的、原则、要素和程序，指出独立的伦理审查对于保护受试者利益的积极意义，并就我国如何推进医学伦理审查工作提出几点建议。     

头孢克洛在中国健康志愿者体内的群体药代动力学研究

目的:建立头孢克洛口服给药在健康志愿者体内的群体药代动力学模型,探讨个体因素对代谢反应的影响。方法:基于头孢克洛生物等效性试验数据,应用非线性混合效应模型的群体方法分析头孢克洛口服给药的生物等效性试验数据,估算相关药代动力学参数及变异。结果:头孢克洛在健康志愿者中符合一级吸收的二室模型。药物表观清除率(CL)、中央分布容积(V2)、中央分布容积(V3)、吸收速率常数(KA)的群体典型值分别为0.219L/min、35.9L、598L和0.042min-1。体重对清除率(CL)有显著影响。结论:群体药代动力学最终模型可对个体药代参数做出精确的估计,体重对表观清除率有影响。     

福多司坦在健康受试者体内的药代动力学

目的研究健康受试者单剂量及多剂量口服福多司坦片后的药代动力学特征。方法36名健康受试者随机分为高、中、低3个剂量组，每组12人，男女各半，分别单剂量口服福多司坦片600，400和200 mg；中剂量组受试者单次口服福多司坦400 mg后，经过1周清洗期，再每日3次，每次400 mg，连续服药5 d。测定血浆中福多司坦的浓度，计算药代动力学参数。结果高、中、低3个单剂量组福多司坦的消除半衰期及体内平均驻留时间相近，AUC_{0-10 h}和C_max均与剂量呈线性关系；男性受试者的T_max，C_max和AUC均小于女性受试者，T_1/2均大于女性受试者。统计学结果表明男性与女性间C_max和AUC的差异与性别无关，而与体重有关。中剂量组多次给药后的平均稳态血药浓度为(4.1±0.8) μg·mL^-1，消除半衰期为(2.5±0.4) h。结论剂量在200～600 mg时，福多司坦在健康受试者体内呈线性药代动力学特征，多剂量给药与单剂量给药的药代动力学参数基本一致。     

阿莫达非尼片在健康受试者体内的药代动力学研究北大核心CSCD

目的研究单剂量口服阿莫达非尼片在中国健康受试者体内的药代动力学和安全性。方法用单中心、随机、开放、三剂量、三周期自身交叉的试验设计,筛选12例健康受试者并随机分组,分别接受单剂量空腹口服阿莫达非尼片100,200,400 mg。用LC-MS/MS法测定血浆中药物浓度,药代动力学参数用DAS 2.1.1软件。结果阿莫达非尼片100,200,400 mg剂量组的主要药代动力学参数如下:t1/2分别为(11.96±1.37),(12.66±1.56),(13.13±1.05)h,tmax分别为(2.41±1.43),(2.50±1.28),(3.00±1.37)h,Cmax分别为(3117±715.80),(5952±1183),(11522±2821)μg·L^(-1)。AUC0-t分别为(535.49±126.21)×10~2,(1081.53±241.91)×10~2,(2268.71±564.30)×10~2h·μg·L^(-1),AUC0-∞分别为(553.66±124.27)×10~2,(1105.26±250.90)×102,(2293.59±565.52)×10~2h·μg·L^(-1)。结论口服阿莫达非尼100~400 mg在人体内的药代动力学过程符合线性药代动力学特征。12例受试者服药后较安全。     

Weight of financial reward in the decision by medical students and experienced healthy volunteers to participate in clinical trials

Summary The aim of this survey was twofold: to assess the willingness of medical students to volunteer for clinical trials and to evaluate the weight of the financial reward and other general details as seen by healthy volunteers who had already participated in clinical trials. A specific questionnaire was given to each group to be answered anonymously. Among the medical students only 2.9% had already volunteered, 39.7% said that they would never participate, 24.7% would do it for scientific interest, 32.2% for scientific interest and financial reward, and 4.2% for the financial reward alone. In experienced volunteers, financial reward was the main reason to participate (90%) followed by curiosity (6.3%). The financial reward actually received was considered adequate compensation for the time and discomfort by most of the volunteers (83.7%). The information supplied by the research team and the arrangements made to treat any hazardous event were considered adequate (47.5%) or optimal (42.5%). Almost all the experienced volunteers (93.8%) answered positively when asked about participation in future studies. The results show that financial reward is a very important reason for healthy volunteers to participate in clinical trials.     

来氟米特在中国健康人群中的群体药动学研究

目的：建立来氟米特口服给药在中国健康受试者体内的群体药动学模型,探讨其药动学特征及可能的影响因素。方法：21名健康男性受试者参与本次研究,应用Phoenix NLME（Vision 8.0）软件中的群体模块分析来氟米特口服给药后其代谢产物的血药浓度数据,估算相关药动学参数及其变异情况。结果：来氟米特活性代谢产物特立氟胺在健康志愿者中符合一级吸收的一室模型。吸收速率常数K_a、分布容积V、药物清除率CL的群体典型值分别为0.691 h^-1、12.843 L和0.031 L·h^-1。协变量筛选结果显示,BMI对分布容积V有显著影响（P<0.01）。结论：本研究成功建立了来氟米特在中国健康人群中的群体药动学模型,最终模型可对个体药代参数做出精确的估计,BMI对分布容积V有显著影响。     

The pharmacokinetics of ofloxacin in healthy adult male volunteers

Conclusion In healthy subjects ofloxacin pharmacokinetics were found to be linear in the dose range studied (100–400 mg). The terminal half-time was 7.5–8 h and plasma ofloxacin concentrations were still detectable at 16 and 24 h after administration. The ratio of renal ofloxacin clerance: creatinine clearance was 1.35–1.82 and was not significantly different for the three doses. The non-renal clearance of ofloxacin was 40–60 ml·min^–1, i.e. 20–30% of the total body clearance.Food intake delayed the absorption of ofloxacin but did not significantly modify its elimination.     

注射用重组人甲状旁腺激素人体耐受性和单剂量药动学研究

目的观察注射用重组人甲状旁腺激素(1-34)[rhPTH(1-34)]在中国健康受试者中的安全性及单剂量药动学特征。方法采用随机、开放的试验设计,耐受性试验将符合入选标准的30名健康男性和女性受试者随机分为5组,每组6名,分别给予rhPTH(1-34)5、10、20、40、60μg,观察临床生命体征及实验室检查指标的变化。单剂量药动学试验将入选的9名健康男性和女性受试者随机分为3组,分别给予rhPTH(1-34)10、20和40μg,3次给药期间有3 d的清洗期。结果rhPTH(1-34)在剂量5～60μg范围内仅有轻度的不良反应发生,给药前后生命体征和实验室检查均无有临床意义的变化,说明在中国健康受试者中的安全性和耐受性良好。3组的剂量、c_(max)、AUC之比分别是0.5:1:2,0.97:1:0.95,1.01:1:0.89,呈良好的线性关系。结论注射用rhPTH(1-34)在剂量5～60μg范围内安全,且呈线性动力学特征。     

Single dose pharmacokinetics of sumatriptan in healthy volunteers

Sumatriptan is classified as a vascular 5HT₁ receptor agonist and is effective in the acute treatment of migraine and cluster headache. Sumatriptan is available as an injection for subcutaneous administration and as a tablet for oral administration. The pharmacokinetics of sumatriptan differ depending on the route of administration.The mean subcutaneous bioavilability is 96% compared to 14% for the oral tablet. The lower bioavailability following oral administration is due mainly to presystemic metabolism. The inter-subject variability in plasma sumatriptan concentrations is greater following oral administration and a faster rate of absorption of drug into the systemic circulation is achieved following subcutaneous dosing. The pharmacokinetics of sumatriptan are linear up to a subcutaneous dose of 16 mg. Following oral dosing up to 400 mg, the pharmacokinetics are also linear, with the exception of rate of absorption, as indicated by a dose dependent increase in time to peak concentration.Sumatriptan is a highly cleared compound that is eliminated from the body primarily by metabolism to the pharmacologically inactive indoleacetic acid analogue. Both sumatriptan and its metabolite are excreted in the urine. Although the renal clearance of sumatriptan is only 20% of the total clearance, it exceeds the glomerular filtration rate, indicating that sumatriptan undergoes active renal tubular secretion. Sumatriptan has a large apparent volume of distribution (170 1) and an elimination half-life of 2 h.Oral doses of sumatriptan were administered as a solution of dispersible tablets and subcutaneous dosing was by injection into the arm. In clinical practice, sumatriptan is administered as a film coated tablet or by subcutaneous injection into the thigh.     

Population pharmacokinetics of arginine glutamate in healthy Chinese volunteers

1.?The present study developed population pharmacokinetic models of arginine and glutamate in healthy Chinese volunteers. Two nonlinear mixed-effect models were developed using NONMEM® software (ICON Development Solutions, Ellicott City, MD) to describe the pharmacokinetic properties and to assess the relevant parameters as well as the inter-individual variability. The potential covariates were screened using stepwise approach and the stability and predictive capability of the models were performed using bootstrap and visual predictive check.

2.?The concentration time curves of arginine and glutamate were best described by a first-order elimination two-compartment model and a nonlinear elimination one-compartment model, respectively. The final parameter estimation of arginine for CL was 44.1?L/h. Q, V₁ and V₂ were 23?L/h, 20.3?L and 46?L, respectively. The final parameter estimation of glutamate for V_max and K_m were 18.8?mg/h and 77.2?mg/L, respectively. V for low dose and high dose was 23.1?L and 36.3?L, respectively.

3.?For arginine, weight was significant covariate on the apparent distribution volume of peripheral compartment. The gain in weight remarkably increases V_2. For glutamate, dose as a significant covariate on the apparent distribution volume was included, subjects received high dose (20?g) have remarkably higher V compared to subjects received low dose (10?g).     

Dose-dependent pharmacokinetics of aprindine in healthy volunteers

Summary The disposition of aprindine following a single oral dose can best be described by a two-compartment open model. The mean plasma half-life (t_1/2) increased from 8.0±2.1 h (SD) after a 25 mg dose to 9.4±2.9 h after 50 mg and to 15.8±2.6 h after 100 mg, with a decrease in total plasma clearance (Cl/F) and volume of distribution at steady state (V_dss/F) and during -phase (V_d/F). The area under plasma concentration-time curve (AUC), maximum plasma concentration (C_max) and the amount of unchanged aprindine excreted in the urine increased in a non-linear fashion with the increase in dose. The t_1/2 after multiple oral doses showed a 3-fold increase over the single dose value. These results indicate that aprindine shows dose-dependent non-linear kinetics.     

The pharmacokinetics of d-sotalol and d,l-sotalol in healthy volunteers

Summary The pharmacokinetics of d-sotalol has been studied in six healthy volunteers given single doses of 0.25, 0.50, 1, 2 mg·kg^–1 i.v. and one 100 mg oral dose in comparison with the kinetics of 1 mg·kg^–1 i.v. of dlsotalol.There was no significant difference in the disposition of the d-enantiomer and the racemate.The terminal half-life averaged 7.2 h, and the kinetics was linear, with a mean total clearance of 0.13 l·h^–1·kg^–1. Renal clearance of d-sotalol represented 56 to 77% of total clearance. The absolute systemic availability of oral d-sotalol was close to 100% and the elimination half-life of the oral-d-enantiomer was similar to that of the i.v. form (7.5 h).     

The pharmacokinetics and pharmacodynamics of medifoxamine after oral administration in healthy elderly volunteers

The pharmacokinetics and psychomotor effects of medifoxamine, a 5 HT reuptake inhibitory antidepressant, were studied in healthy elderly volunteers after single and multiple dosing.The elimination half life (t1/2z) after single doses of 300 mg was 2.8 h — almost identical to that found in young volunteers. After seven days of dosing at 100 mg three times daily the mean corrected AUC after 300 mg significantly increased from 1.04 to 1.34 mg.h.l^–1 and t1/2_z increased to 4.0 h (NS).There were no significant changes in critical flicker fusion frequency, symbol digit substitution, continuous attention or choice reaction times.     

Influence of fluconazole on the pharmacokinetics of omeprazole in healthy volunteers

Influence of fluconazole on the pharmacokinetics of omeprazole was evaluated by single oral administration of omeprazole capsule 20 mg (control group), or single oral administration of fluconazole capsule, 100 mg, and omeprazole, 20 mg, after 4 days of daily oral administration of fluconazole, 100 mg (treated group), to 18 healthy male volunteers. Omeprazole is extensively metabolized in the liver through 5-hydroxylation and sulfoxidation reactions catalyzed predominantly by CYP2C19 and CYP3A4, respectively. Fluconazole is a potent competitive inhibitor of CYP2C19 and a weak inhibitor of CYP3A4. In treated group, the area under the plasma concentration-time curve of omeprazole from time zero to time infinity (AUC) was significantly greater (3090 vs 491 ng h/ml), terminal half-life of omeprazole was significantly longer (2.59 vs 0.85 h), and peak plasma concentration of omeprazole (C(max)) was significantly higher (746 vs 311 ng/ml) than that in control group. The greater AUC and higher C(max) in treated group could be due to inhibition of omeprazole metabolism by fluconazole.