Pharmacokinetics of phenprocoumon in man investigated using a gas chromatographic method of drug analysis

Summary A gas chromatographic method for the determination of phenprocoumon (Marcumar^®) in serum and urine is described, which facilitates accurate values down to 0.5 g phenprocoumon/ml serum. After the i.v. administration of 20 mg phenprocoumon in a single dose to 4 healthy volunteers the following pharmacokinetic data were obtained:After the initial fast decrease (phase 1) of the serum level of phenprocoumon, probably due to the distribution into the different compartments is followed by a subsequent slower fall (phase 2) which occurs with a serum half-life of 157 h. The apparent distribution volume was 6.51. Analysis of the urine demonstrated that 90% of the excreted phenprocoumon detected was in the glucuronide form.This study was supported by a grant from the Deutsche Forschungsgemeinschaft.Preliminary reports were presented on March, 19, 1973 at the 14th Spring Meeting of the Deutsche Pharmakologische Gesellschaft in Mainz and on May 2, 1973 at the 79th Congress of the Deutsche Gesellschaft für innere Medizin in Wiesbaden.     

布比卡因白蛋白微球的制备及药理学研究

目的制备盐酸布比卡因人血清白蛋白微球(Bupi-HSA-MS),并对其体内药动学、药效学及生物相容性进行评价。方法采用高压电场法制备布比卡因人血清白蛋白微球,采用改良的反相高效液相色谱法测定体内布比卡因血药浓度,以家兔为实验对象,以针刺疼痛反应圈直径大小评价其麻醉效果。结果药动学实验结果表明,注射剂组血药浓度达峰值时间短,浓度高,药物驻留时间短。微球组峰值浓度显著低于注射剂组并长时间维持低浓度。微球组MRT较对照组明显延长(P<0.01)。微球组皮下给药最大麻醉圈直径明显小于注射剂对照组(P<0.01),而微球组局麻持续时间较对照组明显延长(P<0.01)。结论高压电场法是一种简单、易行的白蛋白微球制备新方法。Bupi-HSA-MS兔皮下给药,药物扩散少,局部麻醉作用持续时间长,是一种安全长效的局部麻醉止痛新方法。     

芦氟沙星胶囊的人体药动学研究

目的:测定盐酸芦氟沙星胶囊在人体内的药动学参数,为临床合理用药提供依据.方法:6例健康志愿者口服盐酸芦氟沙星胶囊200 mg后于不同时间取血,用高效液相色谱法(HPLC)测定血浆中芦氟沙星的血药浓度,按3P87药动学程序处理.结果:盐酸芦氟沙星胶囊口服后符合血管外口服一室开放模型,Tmax为(1.53±0.34) h,Cmax为(1.93±0.41) mg&#8226;L 1,浓度 时间曲线下面积(AUC)为(99.67±10.71) mg&#8226;h&#8226;L 1,t1/2为(34.16±8.55) h.结论:芦氟沙星血药浓度高,组织分布广,具有良好的药动学特征.     

脂质体肺部给药的研究

由于脂质体肺部给药具有刺激性小、吸收迅速、生物利用度高、安全性好、可实现持续缓慢释药等独特优势而成为近年来制剂领域的研究热点之一。本文论述脂质体肺部给药的特点、稳定性以及在药代动力学、药效学和安全性等方面的最新研究进展。     

头孢哌酮 /三唑巴坦复方制剂的人体药代动力学研究

目的研究静脉滴注头孢哌酮/三唑巴坦复方制剂(800mg/200mg)与头孢哌酮(800mg)在健康志愿者中的药代动力学。方法10名健康志愿者分别随机交叉静脉滴注头孢哌酮/三唑巴坦复方制剂1600mg/400mg和对照药头孢哌酮1600mg,用反相高效液相色谱法分别测定头孢哌酮和三唑巴坦血药浓度和尿中的药物浓度,计算两药的药代动力学参数,比较复方制剂两组分有无药代动力学的相互作用。结果试验药和参比药中头孢哌酮的血药峰浓度Cmax分别为(181.52±39.94)、(176.21±32.66)mg/L;消除半衰期t1/2β分别为(2.23±0.67)、(2.28±0.61)h;药时曲线下面积AUC0.5-12分别为(351.96±54.53)、(336.31±54.93)mg·h/L,AUC0-12分别为(402.21±57.6)、(376.64±55.18)mg·h/L,AUC0-inf分别为(413.47±59.06)、(395.83±62.08)mg·h/L;24h尿药累积排泄百分率分别为(22.92±7.79)%、(21.00±7.33)%。三唑巴坦的峰浓度Cmax为(20.31±4.76)mg/L,药时曲线下面积AUC0.5-5为(12.96±2.40)mg·h/L,AUC0-5为(18.45±3.52)mg·h/L,AUC0-inf为(19.42±3.67)mg·h/L;消除半衰期t1/2β为(0.84±0.28)h;24h尿药累积排泄百分率为(60.56±19.37)%。结论两种制剂中,头孢哌酮的主要药代动力学参数Cmax、t1/2β及AUC经双单侧检验无显著性差异(P>0.05),三唑     

Poloxamer gel as vehicle for transdermal iontophoretic delivery of arginine vasopressin: evaluation of in vivo performance in rats

The present study describes the formulation and evaluation for pharmacokinetic and pharmacodynamic activity of arginine vasopressin (AVP), a nanopeptide with antidiuretic activity on being delivered by transdermal iontophoresis. Poloxamer 407 was used to form stable gels that did not reduce the release of AVP. The release rate from the gel followed Higuchi kinetics indicating that the dominant mechanism of release is diffusion. Iontophoresis alone and in combination with chemical enhancers was used to augment the transdermal permeation of AVP. The results of both pharmacokinetic and pharmacodynamic studies emphasize the dimension of 'rapid onset' achieved by iontophoresis. The correlation between pharmacokinetic data and pharmacodynamic activity was only qualitative. Histopathological studies revealed that skin toxicity caused by either iontophoresis or chemical enhancers when used alone could be reduced by using a combination of both the techniques in tandem.     

Drug discovery information integration: virtual humans for pharmacokinetics

The ‘virtual human’ refers to simulation models based on explicit mathematical models of mammalian physiology. When applied to pharmacokinetics (PK), the virtual human embodies models that can be parameterised for different species, different individuals and populations of individuals, and that allow simulation of PK from measured and/or predicted in vitro properties. The models are independent of the properties of any specific drug, and can be used for the prediction of drug behaviour in specific human individuals and in pre-clinical species. The hope is that these models will allow the prediction of PK throughout the drug discovery and development process, enabling effective targeting of synthetic chemistry efforts to compounds with the required therapeutic effect, careful evaluation of multiple candidates for development, assessment of the potential for drug-drug interactions, evaluation of multiple formulations, efficient clinical trial design and other benefits, including reduction of animal usage in drug discovery. However, we believe that the biggest impact on drug discovery productivity would accrue from achieving two clear objectives: an estimate of human in vivo activity on every compound synthesised and a reliable prioritisation, based on predictions of human in vivo activity, for the next round of synthesis. It is realistic to believe that the benefits of delivering these objectives could, through shortening the time to decision and increasing the chance of success, lead to a five- to ten-fold increase in discovery output. It is also now possible to demonstrate that a combination of virtual human simulation software and industrial-scale absorption, distribution, metabolism and elimination (ADME) testing can deliver both of these objectives.     

HPLC-MS法测定犬血浆中环维黄杨星D浓度及其药代动力学研究

目的 :建立用于测定环维黄杨星D血药浓度的液相色谱 质谱联用分析方法 ,并探讨环维黄杨星D在犬体内的药代动力学。方法 :犬 5只ig环维黄杨星D 10mg·kg-1后采集一系列血样 ,利用HPLC MS(TOF)法 ,测定血浆药物浓度 ,并用 3p97软件拟合求算药代动力学参数。结果 :环维黄杨星D浓度在 0 5～ 2 0 0ng·ml-1线性关系良好 (r=0 9999)。提取回收率高于 80 % ,日内、日间RSD均小于 15 % ,符合生物样品分析要求。 5只犬ig环维黄杨星D 10mg·kg-1后的血药浓度 时间曲线呈二室模型 ,其吸收相、分布相和末端消除相的半衰期 (t1/ 2Ka、t1/ 2α和t1/ 2 β)分别为 1 72 ,2 82 ,14 90h ,曲线下面积 (AUC)为 1372 5± 2 19 4ng·h·ml-1。结论 :建立的HPLC MS联用方法专属性强 ,灵敏度高 ,可用于环维黄杨星D的体内定量分析。     

中国健康志愿者单剂口服甲磺酸加替沙星片的药代动力学研究

目的研究中国健康成年志愿者单剂口服甲磺酸加替沙星片的药代动力学。方法按GCP指导原则设计试验方案,选择9名健康受试者分别依次单剂口服200、400、600mg三个剂量的甲磺酸加替沙星片后,应用HPLC测定血药浓度,采用3P97软件进行数据处理,求出药代动力学参数。结果受试者分别给药后,药-时曲线符合二房室模型,主要药代动力学参数Cmax分别为(2.028±0.362)mg/L、(3.749±0.446)mg/L、(4.876±0.569)mg/L;t1/2β分别为(7.489±0.806)h、(7.063±0.890)h、(7.735±0.8701)h;AUC0-t分别为(12.24±1.51)mg·h/L、(26.02±3.38)mg·h/L、(39.22±6.57)mg·h/L;原型药主要经肾排泄,48h尿药累积排泄率分别为(61.90±7.70)%、(60.90±5.70)%和(58.74±13.49)%。结论9名健康受试者分别口服给药后,药-时曲线符合二房室模型,甲磺酸加替沙星在200～600mg剂量范围内药物体内过程呈线性动力学特征而无饱和性,主要排泄途径为肾脏。     

甲状腺功能对磺胺嘧啶在大鼠体内药动学的影响

目的: 测定不同甲状腺功能状态时大鼠血液中磺胺嘧啶钠(SD)的浓度,研究甲状腺功能状态对其药代动力学的影响.方法: 采用分光光度计比色法测定技术.结果: 甲亢组大鼠磺胺嘧啶在体内消除加速,峰浓度下降,AUC减少,消除t1/2缩短.甲减组大鼠则消除减慢,峰浓度增高,AUC增大,消除t1/2延长.结论: 甲状腺功能提高时,大鼠对磺胺嘧啶的代谢能力明显增加,消除加速;而甲状腺功能降低则相反.