利奈唑胺群体药动学的文献分析

利奈唑胺是临床常用的抗革兰氏阳性菌感染药物,其个体间药动学差异大。本文通过查阅当前发表的利奈唑胺群体药动学文献,提取建模相关信息并进行分析归纳与综述,以期为利奈唑胺的临床用药提供参考。相关文献表明利奈唑胺代谢的主要影响因素为体重、年龄、肌酐清除率和肾小球滤过率,临床制订给药方案时应优先考虑这些因素。     

中药临床药动学的研究现状与思考

目的:加强中药临床药动学的研究,指导临床合理用药。方法:分析近年来中药药动学、中药临床药学的研究现状,提出中药临床药动学的思考与展望。结果与结论:中药临床药动学的研究可为临床合理用药提供可量化的数据和证据,深入开展该项工作显得尤为重要。     

成人万古霉素群体药动学的研究进展

目的:为临床合理应用万古霉素提供参考。方法:以"成人""万古霉素""群体药动学""群体药动学模型""Adults""Vancomycin""Population pharmacokinetic""PPK model"等为中英文关键词,在PubMed、中国知网、万方等数据库中组合检索自建库起至2019年10月31日发表的相关文献,对成人万古霉素群体药动学(PPK)的研究进展进行综述。结果与结论:共检索到相关文献166篇,其中有效文献25篇。目前已有研究在成年感染患者、危重症患者、接受肾脏替代治疗及血液滤过治疗的患者、神经外科患者、接受体外膜氧合治疗的患者、重症脓毒血症患者、血液肿瘤患者以及下呼吸道感染重症患者等群体中建立了万古霉素PPK模型。成人患者中,肌酐清除率与体质量是影响万古霉素药动学参数的主要因素,提示临床用药时应当关注患者肾功能与体质量;另外,是否感染及感染类型也对万古霉素的药动学参数有不同程度的影响。对于接受肾脏替代治疗及血液滤过治疗的患者,万古霉素的清除主要与其疗法的滤过率相关,提示临床应当根据所接受疗法的滤过率调整剂量;对于神经外科患者,脑脊液白蛋白与脑脊液引流量则是万古霉素脑脊液分布与清除的主要协变量,提示临床在脑脊液白蛋白低以及脑脊液引流量大时,应适当增加给药剂量。此外,患者的年龄、性别也是药动学参数的影响因素之一。在不同人群中,万古霉素药动学参数差异较大,应结合不同人群中的各类影响因素来制定合理的给药方案。     

癫痫病药物治疗新进展

综述近年出现的一些新型抗癫痫药的作用机制、药动学、用法用量、药物不良反应、药物相互作用及临床治疗应遵循的原则,为临床合理应用抗癫痫药提供用药依据.     

药师下临床的体会

药师参与临床用药是势之所趋，向临床医生、护士提供临床药物使用咨询，收集药物的不良反应，开展临床药动学的研究、进行个体化给药，可明显提高临床药品应用的水平和降低药品不良反应。     

麦考酚酸制剂体内药动学参数、临床疗效及不良反应影响因素的研究进展

目的:了解麦考酚酸(MPA)制剂体内药动学参数、临床疗效及不良反应影响因素的研究进展,为临床合理用药提供循证依据。方法:查阅近年来国内外文献,从基因多态性、患者机体因素和药物因素等方面对MPA的体内药动学参数、临床疗效和不良反应的影响进行归纳和总结。结果与结论:吗替麦考酚酯(MMF)和麦考酚钠(EC-MPS)为MPA的2种常用制剂。MMF为器官和组织移植术后抗免疫排斥反应的一线用药,其体内药动学参数、临床疗效和不良反应发生率受基因多态性、患者机体因素(种族、血清白蛋白水平、术后时间和并发症等)和药物因素(联合用药、药物剂型和给药剂量)等影响。     

用离子对-HPLC法测定人血清中去甲万古霉素的血药浓度

去甲万古霉素（norvancomycin）是糖肽类抗生素，临床上主要用于严重的G＋菌感染，特别是耐甲氧西林的金黄色葡萄球菌感染和表皮葡萄球菌感染。但其人体内药动学个体差异明显，且易发生听神经损害和肾毒性等严重不良反应，临床应用时必须严格控制适应证及其用法用量，加强用药监护，并进行血药浓度监测。去甲万古霉素血药浓度测定方法目前国内外已有许多相关报道，但未见离子对-HPLC法的报道。采用离子对-HPLC法以依诺沙星为内标测定人血清中去甲万古霉素的浓度，方法稳定，操作简便，适合临床血药浓度监测和体内药动学研究。     

常用药动学公式的拓展及应用

目的:应用药动学理论指导临床合理用药。方法:对基本药动学公式进行拓展和转换,得到临床实用的新公式;创建实用药动学参数表,应用该表得到临床需要的药动学参数。结果:有了实用药动学参数表,随时可考察临床用药的合理性,结合血药浓度监测,可做到用药个体化。结论:实用药动学参数表可作为指导个体化用药的重要工具。     

碘海醇注射液的安全性评价和风险管理研究

目的:评价碘海醇注射液的临床总体安全性,分析碘海醇致不良反应发生的规律和特点,提出碘海醇注射液临床使用的风险管理建议。方法:对比分析碘海醇注射液的国内外药品说明书,汇总评价北京市药品不良反应监测中心数据库中近5年碘海醇注射液药品不良反应报告,制定碘海醇临床使用的风险管理策略。结果:经评价,国内外不同厂家碘海醇注射液的说明书存在明显差异,尤其是不良反应方面。在212例碘海醇注射液不良反应报告中,老年人不良反应的发生率较高,主要累及皮肤及附件、循环系统、消化系统等,其中皮肤及附件的损害最常见,占57.1%,主要表现为皮疹、荨麻疹和瘙痒等。严重不良反应为过敏性休克、肾功能异常等。结论:碘海醇注射液是临床应用广泛的非离子型造影剂,不良反应较明确。应通过加强医院层面的行政干预和宣传教育等措施,规范碘海醇注射液的操作流程,提倡多科室合作的用药监护,保障碘海醇注射液的临床用药安全。     

1例血液滤过患者万古霉素持续滴注给药的病例分析

临床药师参与1例经血液滤过治疗患者的导管相关感染、肺感染的诊疗过程.分析万古霉素持续滴注的药代与药动学、不良反应的发生率、稳定性等方面因素.提出对于该患者建议使用持续滴注方式给药并同时进行血药浓度监测使患者的感染得到控制.通过探讨万古霉素持续滴注给药方式的适宜性,可为相关人群的安全用药提供科学依据.     

Contrast media and glomerular filtration: dose dependence of clearance for three agents

Determination of plasma clearance of contrast agents has been advocated as a means to assess glomerular filtration rate. To evaluate the feasibility of different agents for this purpose, we have compared, in healthy volunteers, the dose dependence of plasma clearance for three contrast media (iohexol, a nonionic agent, and iothalamate and metrizoate, which are ionic substances), with special emphasis on the lower dose range (2-20 mL corresponding to 0.9-12.9 g, depending on dose and agent). Iohexol and iothalamate were cleared at constant rates, irrespective of given dose, whereas metrizoate clearance increased significantly at lower doses. In general, the clearances or iothalamate and metrizoate were, respectively, moderately and markedly higher than that of iohexol. The clearance of different doses of metrizoate (2 mL versus a radiographic dose of 40 mL or more) was also compared with the clearance of [51Cr]EDTA in two groups of patients with reduced renal function. When compared with [51Cr]EDTA in patients with renal dysfunction, metrizoate was cleared significantly faster after a 2-mL dose, whereas clearances were identical when the metrizoate dose was 40 mL or more. These findings indicate that tubular secretion plays an active role in the elimination of metrizoate. The pharmacokinetic properties of iohexol, in combination with its low toxicity, make it a suitable agent for determination of glomerular filtration rate in clinical practice.     

Method development for determining the iohexol in human serum by micellar electrokinetic capillary chromatography

Iohexol is widely used in clinical laboratories as a non-ionic radiographic contrast medium. Determination of its concentration in blood has a vital meaning in preventing its side effects caused by its retention in the system. A method for determining iohexol in serum by micellar electrokinetic capillary chromatography (MECC) requiring no pretreatment is developed. Electrophoresis is performed for serum samples at 25 kV with a borate buffer (50mM; pH 9.5) containing sodium dodecyl sulfate (50mM) and detection is carried out at 245 nm. Migration time of iohexol is 7.4 min. Linearity (0-1000 mg/l) is good and detection limit is 0.5mg/l (S/N=3). CV of intra-assay precision at a measurement concentration range of 6.2-200.1mg/l is 1.38-4.68% and recovery rate is 96-102%. CV of inter-assay precision is 2.06-5.94% at a measurement concentration range of 10.3-155.4 mg/l. This method is characterized by determination through direct injection of serum samples of super micro-quantity into the capillary, which simplifies the determination procedure in a significant manner and improves the precision and accuracy of determination.     

Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and p-aminohippuric acid.

The objective of this study was to validate a kinetic approach for the simultaneous measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in the dog. Six healthy male Beagle dogs were randomly assigned in a three-period cross-over study of intravenous bolus administration of iohexol (64.7 mg/kg), PAH (10 mg/kg), and an iohexol/PAH mixture. PAH and iohexol were determined simultaneously by a validated high-performance liquid chromatographic method. The iohexol and PAH data obtained after intravenous administration were analyzed using noncompartmental and bicompartmental approaches. A simplified iohexol plasma clearance was also calculated from the terminal elimination phase of the plasma iohexol concentrations versus time profile. The total plasma clearance values for PAH and exo-iohexol were 13+/-2.3 mL/kg/min and 2.9+/-0.3 mL/kg/min, respectively. No significant (or biologically relevant) effect of coadministration of PAH and iohexol was observed on the pharmacokinetic parameters of either drug. The calculation of simplified plasma clearance led to an overestimation of the true plasma clearance. In conclusion, GFR and ERPF can easily and rapidly be measured in the dog by this approach which is relatively noninvasive.     

Glomerular filtration and saturable absorption of iohexol in the rat isolated perfused kidney.

1. The renal handling of iohexol was examined in the rat isolated perfused kidney (IPK) over a perfusate concentration range of 5-20 micrograms ml-1. 2. At a concentration of 5 micrograms ml-1, a ratio of renal clearance over clearance by glomerular filtration (ClR/GF) of 0.63 +/- 0.06 could be determined. This ratio increased until 1.02 +/- 0.06 at 20 micrograms ml-1, indicating that a saturable mechanism is involved in the luminal disappearance of the drug. 3. Pretreatment of the kidneys with polylysine, probenecid or diatrizoate resulted in a significantly enhanced clearance of iohexol, probably due to inhibition of membrane binding. Renal clearance data were fitted to a kinetic model including filtration into the primary urine followed by saturable absorption at the luminal membrane. An absorption constant, KA, of 7.3 +/- 1.3 micrograms ml-1, and a maximum rate of absorption, VA,Max, of 1.4 +/- 0.1 micrograms min-1 were determined. 4. Iohexol accumulated in kidney tissue, reaching a concentration of 2 to 7.5 times the perfusate concentration. In freshly isolated proximal tubular cells and kidney cortex mitochondria, iohexol reduced the uncoupled respiratory rate at a concentration comparable to the highest tissue concentration found in the IPK. 5. In conclusion, iohexol is not only filtered by the kidney but also reabsorbed via a saturable mechanism, which results in tubular accumulation. Intracellularly sequestered iohexol may affect mitochondrial oxidative metabolism. Our results indicate that iohexol is not a true filtration marker.     

Iohexol and iopamidol: second-generation nonionic radiographic contrast media

Iohexol and iopamidol are new second-generation nonionic contrast media. We review their physical/chemical properties and describe the improvements made over the first-generation nonionic prototype, metrizamide, and conventional ionic contrast media. The significance of low osmolar solutions is discussed and the relationship between osmolality and adverse reactions is emphasized. The convenience of a ready-to-use stable solution that offers an advantage over the lyophilized metrizamide in practical application is suggested. Clinical studies using randomized, double-blind comparison techniques are cited. An attempt is made to define the exact role for iohexol and iopamidol.     

碘海醇致严重不良反应65例文献分析

目的：了解碘海醇致严重不良反应（ADR）的情况,分析其特点和相关因素,促进临床合理用药。方法：采用文献学计量方法,对国内公开报道的65例碘海醇致严重ADR进行总结性分析。结果：碘海醇致严重ADR中,全身性损害41例,神经系统损害10例,呼吸系统损害8例,泌尿系统损害3例,皮肤附件、血液及消化系统损害各1例。结论：碘海醇致全身性、神经系统、呼吸系统损害较为多见,占总ADR分别为63.08%,15.38%,12.31%;碘海醇ADR前3位依次为过敏性休克、神经系统和呼吸系统损害,占总ADR78.46%。     

63例碘海醇注射液严重不良反应/事件文献分析

目的 初步分析碘海醇注射液发生严重不良反应/事件的特点及相关因素,为临床合理用药提供参考依据.方法 对中国知网和万方数据库1998年1月至2012年3月发表的文献进行检索,按事先制定的文献纳入标准收集文献,提取其中涉及碘海醇注射液严重不良反应/事件的信息进行分析.结果 纳入文献25篇,安全证据等级主要为3b和2b;涉及病例63例,均为成人,其中以中老年患者居多;不良反应的临床表现主要为造影剂肾病、休克和过敏样反应.结论 应加强对碘海醇注射液的监测,药品生产企业应开展大规模的流行病学研究,探索碘海醇临床使用中的保护性因素和风险因素,进一步完善说明书,为控制临床使用风险提供科学依据.     

碘海醇致1例严重神经系统不良反应并文献复习

目的：提高对碘海醇神经系统严重不良反应的认识。方法：报告1例超剂量使用碘海醇行腰椎脊髓造影术致患者出现脑病病例,并进行文献复习。结果：碘海醇具有神经系统毒性,过量使用加大出现严重不良反应的风险。结论：使用碘海醇之前,告知患者及家属风险,了解患者过敏史,签署知情同意书,做好急救准备,有助于减少可能出现的不良反应和医患纠纷。     

Noninvasive monitoring of local drug release using X-ray computed tomography: optimization and in vitro/in vivo validation

In vivo release profiles of drug-loaded biodegradable implants were noninvasively monitored and characterized using X-ray computed tomography (CT). The imaging method was adapted and optimized to quantitatively examine the release of an active agent from a model cylindrical PLGA device (the millirod) into rabbit livers over 48 h. Iohexol, a CT contrast agent, served as a model drug; optimization of CT acquisition parameters yielded a sensitivity of 0.21 mg/mL (or 95 microg iodine/mL) for this agent. In vitro validation of the method was carried out by tracking release of iohexol in gelatin gel phantoms. In vivo release in rabbit livers was characterized through quantitative analysis of CT images and compared with UV-Vis analysis of the explanted devices at three implantation times. After correction for respiratory motion, CT analysis correlates well with the extracted iohexol data at all time points. The percent error between the actual and experimental image data was below 10%. This study demonstrates the potential of using computed tomography to noninvasively quantify the rate of agent release from controlled delivery devices in vivo.