Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of furosemide

The pharmacokinetics and pharmacodynamics of furosemide were evaluated after intravenous administration of the same total dose of furosemide in different lengths of infusion time (10 s, 30 min, 2 h, and 8 h) to 6 dogs. The fluid loss in urine was immediately replaced volume for volume with intravenous infusion of Lactated Ringer's solution. The pharmacokinetic parameters such as per cent of the dose excreted in urine, total body and renal clearances, and terminal half-life were not significantly different with four different infusion times. The volume of distribution at steady state and mean residence time based on venous data, on the other hand, appeared to increase with increasing infusion time. The mean values for Vss were 0.334, 0.478, 0.499, and 0.708 1 kg-1 for 10 s, 30 min, 2 h, and 8 h of infusion, respectively, and the corresponding values for MRT were 17.5, 22.2, 24.8, and 38.1 min. The diuretic effects (urine output and urinary excretion of sodium) were generally found to increase with increasing infusion times; the total mean 24 h urine outputs were 1102, 1464, 2190, and 3470 ml for 10 s, 30 min, 2 h, and 8 h of infusion, respectively, and the corresponding values for sodium excretion were 170, 175, 272, and 440 mmol. Furosemide plasma concentrations and hourly urinary excretion rates of furosemide, sodium, and potassium during the apparent steady state (between 2 and 8 h) in the 8 h infusion study were fairly constant.     

Linear pharmacokinetics of haloperidol in the rat.

Pharmacokinetics of haloperidol in the rat following intravenous bolus doses of 0.5, 1.0, and 2.5 mg kg-1, respectively, were investigated. It was found that haloperidol was a high extraction ratio drug with a total blood clearance averaging 83 ml min-1 kg-1. The volumes of distribution were large with a mean of 5.5 1 kg-1 (Vc), 11.11 kg-1 (V beta), and 9.61 kg-1 (Vss), respectively. The terminal half-life was 1.5 h. The disposition kinetics of haloperidol was found to be linear over the dose range studied. After constant intravenous infusions of haloperidol by different infusion rates during 12 h, steady-state levels were reached in the blood. The measured steady-state blood concentrations were consistent with those predicted by a biexponential infusion model based on the parameters obtained from the intravenous bolus study. The total blood clearance at steady-state was concentration-independent within the investigated range of 5 to 20 ng ml-1.     

Pharmacokinetics of isosorbide dinitrate after intravenous infusion in human subjects

Plasma concentrations of isosorbide dinitrate have been measured after intravenous infusion of drug at a rate of 5·0 mg h^?1 for 150 min and after single equal oral doses of 12·5 mg of drug in solution to two normal human subjects. During the infusion, uneven plateau concentrations were approached after 30 min. The calculated average steady-state plasma levels were 258 ng ml^?1 and 514 ng ml^?1 in the two subjects respectively. The half-life of elimination of isosorbide dinitrate after termination of the infusion was 9–10 min. After oral doses, peak plasma levels of 26·6 ng ml^?1 and 12·7 ng ml^?1 occurred at 10 min and 20 min in the two subjects respectively. The terminal half-life of drug after the oral doses was much longer than the elimination half-life (about 10 min), and was associated with the absorption phase. Fairly good agreement was obtained between the observed concentrations and those predicted by a one-compartment open model. The systemic availability of isosorbide dinitrate after the oral doses was up to only 3 per cent of the equal doses infused, indicating that presystemic elimination processes accounted for very large proportions of the oral doses. The systemic clearances of drug after infusion of 0·32 1 min^?1 and 0·161 min^?1 were unexpectedly low for a drug of reported high liver extraction ratio.     

Isosorbide 5-mononitrate pharmacokinetics in humans

When isosorbide 5-mononitrate was intravenously infused at a rate of 4 mg h ^?1 for 2.5 h to five human subjects, its concentrations in plasma increased slowly to 185 ng ml^?1 ± 5 per cent C.V. at 2.5 h and a steady-state plasma level was not reached during the infusion. When the infusion was discontinued, plasma drug concentrations declined with an elimination half-life of 4.2 h ± 6 per cent C.V. The systemic clearance after the infusion doses was 132 ml min^?1 ± 18 per cent C.V. and the volume of distribution was 48.4 1 ± 16 per cent C. V. After equal oral doses of 10 mg, the peak plasma isosorbide 5-mononitrate concentration of 191 ng ml^?1 ±16 per cent C.V. was reached at 1.1 h ± 30 per cent C.V., and plasma levels declined with a terminal half-life of 4.9 h. The complete systemic availability of isosorbide 5-mononitrate indicated that pre-systemic elimination after the oral doses was negligible. A one-compartment open model appeared adequate to describe the plasma level data after intravenous infusion and oral doses. After single oral doses of 10 mg isosorbide dinitrate, the peak plasma concentration of the 5-mononitrate metabolite of 72 ng ml^?1 ± 27 per cent C. V. occurred at l.7h.41 per cent C.V. Approximately 50 per cent (range 22–68 per cent) of the oral dose of isosorbide dinitrate circulated in plasma as the 5-mononitrate metabolite. The pharmacokinetics of isosorbide mononitrates are markedly different to those of the parent dinitrate and these differences follow from the greater systemic availability and volume of distribution of the mononitrates.     

Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of bumetanide

The pharmacokinetics and pharmacodynamics of bumetanide were evaluated after intravenous (i.v.) administration of the same total dose of bumetanide in different lengths of infusion times, 10 s (treatment I), 1 h (treatment II), and 4 h (treatment III) to rabbits. The fluid loss in urine was immediately replaced volume for volume with i.v. infusion of lactated Ringer's solution. Some pharmacokinetic parameters of bumetanide were infusion time-dependent and it might be due to the saturable metabolism of bumetanide. For example, the mean values of CL (13.6, 25.3 vs 18.2 ml min^?1 kg^?1), MRT (9.70, 10.6 vs 21.8 min), V_ss (128, 217 vs 378 ml kg^?1), and CL_NR (2.71, 9.24 vs 6.44 ml min^?1 kg^?1) increased when the same dose of bumetanide was infused in 1 h or 4 h. However, the mean values of t_1/2, and CL_R were not significantly different among three treatments. The diuretic effects (urine outputs and urinary excretions of sodium and chloride) increased significantly in 1 and 4 h of infusion although the total amounts of urinary excretion of unchanged bumetanide were 21.8 and 20.5 per cent lower in treatments II and III, respectively, when compared with the value in treatment I; the mean values of 8-h urine outputs were 373, 922, and 1030 ml for 10s, 1 h, and 4 h of infusion, respectively, and the corresponding values for 24-h sodium excretions were 49.0, 82.8, and 121 mmol, and for chloride were 47.5, 71.1, and 114 mmol. It could be due to the higher diuretic efficiencies in treatments II and III. Plasma concentrations of bumetanide, and hourly urine outputs and hourly urinary excretion rates of bumetanide, sodium, potassium, and chloride during the apparent steady state (between 1 and 4 h) in the 4 h infusion study were fairly constant.     

Population pharmacokinetics of continuous infusion of piperacillin in critically ill patients

Dosing recommendations for continuous infusion of piperacillin, a broad-spectrum beta-lactam antibiotic, are mainly guided by outputs from population pharmacokinetic models constructed with intermittent infusion data. However, the probability of target attainment in patients receiving piperacillin by continuous infusion may be overestimated when drug clearance estimates from population pharmacokinetic models based on intermittent infusion data are used, especially when higher doses (e.g. 16?g/24?h or more) are simulated. Therefore, the purpose of this study was to describe the population pharmacokinetics of piperacillin when infused continuously in critically ill patients. For this analysis, 270 plasma samples from 110 critically ill patients receiving piperacillin were available for population pharmacokinetic model building. A one-compartment model with linear clearance best described the concentration–time data. The mean?±?standard deviation parameter estimates were 8.38?±?9.91?L/h for drug clearance and 25.54?±?3.65?L for volume of distribution. Creatinine clearance improved the model fit and was supported for inclusion as a covariate. In critically ill patients with renal clearance higher than 90?mL/min/1.73?m², a high-dose continuous infusion of 24?g/24?h is insufficient to achieve adequate exposure (pharmacokinetic/pharmacodynamic target of 100% fT_{>4 x MIC}) against susceptible Pseudomonas aerginosa isolates (MIC ≤16?mg/L). These findings suggest that merely increasing the dose of piperacillin, even with continuous infusion, may not always result in adequate piperacillin exposure. This should be confirmed by evaluating piperacillin target attainment rates in critically ill patients exhibiting high renal clearance.     

精密输液器减少输液反应的疗效观察

目的探讨精密输液器减少输液反应的效果和使用安全性。方法实验组120例患儿使用精密滤过输液器,对照组120例患儿使用普通输液器。结果观察组发生不良反应4例,占3.1%,对照组发生不良反应23例,占21.7%,经x2检验,差异有统计学意义(P<0.05)。结论精密输液器能减少不良反应的发生,比普通输液器使用更加安全。     

输液泵输注甘露醇的可行性研究

目的:探讨输液泵输注甘露醇的可行性.方法:随机将输注甘露醇的病人1620例次分为两组,每组810例次,观察组用输液泵输注,对照组采用重力法输入,观察两组外渗发生例次和面积以及外渗的血管部位.结果:两组外渗发生例次和面积差异有统计学意义(P<0.01),观察组的外渗例次多于对照组,外渗面积大于对照组;两组外渗的发生均与选择静脉的直径呈负相关.结论:输液泵不能用于加压输注甘露醇,但在重力法输液的流速能达到甘露醇使用要求时,可用输液泵恒速输入.     

静脉滴注患者1328例使用情况分析

目的 统计分析我院住院部患者静脉滴注的使用情况,以促进临床合理用药.方法 从医院计算机信息管理系统中抽取2010年1～6月住院500例患者中静脉滴注医嘱共1 328份.找出使用不合理的医嘱进行统计分析.结果 在1 328份医嘱中,共有不合理医嘱224份,占全部抽查医嘱的16.9％,临床不合理用药主要表现在:溶媒的选择、药物的配伍、药物的剂量及药物的滴速等方面.结论 我院住院部静脉滴注的使用仍存在一些问题,需要加强管理、规范使用,同时必须充分发挥临床药师的职责,在静脉滴注医嘱审查方面多做工作.     

发热型输液反应残留输液内毒素检查与原因分析

目的探讨患者输液过程中发生的发热型输液反应与输液内毒素限值的关系,为临床输液致发热型输液反应的原因分析提供输液内毒素限值的参考依据。方法依据2005年版《中国药典》（二部附录XI E细菌内毒素检查法）,建立了残留输液、留样输液、外购输液和加药输液的内毒素检查方法,并通过供试品阳性对照、阳性对照和阴性对照等实验验证了方法的可行性和结果的可靠性。结果我院两年来发生的发热型输液反应,剩余输液内毒素含量检查符合规定。结论检查分析认为,所发生的发热型输液反应应排除输液内毒素含量超标因素。反应的发生与患者对内毒素的敏感性,输液中的微粒数,输液速度等可能存在一定关系。     

Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans

Background

Prescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine.

Methods

Plasma was collected for 72 h after administration of placebo or 2, 4, 8, 12, or 16 mg IV buprenorphine in escalating order (single-blind, double-dummy) in 5 healthy male non-dependent opioid users. Buprenorphine and its primary active metabolite, norbuprenorphine, were quantified by liquid chromatography–tandem mass spectrometry with limits of quantitation of 0.1 μg/L.

Results

Maximum buprenorphine concentrations (mean ± SE) were detected 10 min after 2, 4, 8, 12, 16 mg IV: 19.3 ± 1.0, 44.5 ± 4.8, 85.2 ± 7.7, 124.6 ± 16.6, and 137.7 ± 18.8 μg/L, respectively. Maximum norbuprenorphine concentrations occurred 10–15 min (3.7 ± 0.7 μg/L) after 16 mg IV administration.

Conclusions

Buprenorphine concentrations increased in a significantly linear dose-dependent manner up to 12 mg IV buprenorphine. Thus, previously demonstrated pharmacodynamic ceiling effects (over 2–16 mg) are not due to pharmacokinetic adaptations within this range, although they may play a role at doses higher than 12 mg.     

静脉滴注阿奇霉素致不良反应探析

目的:探析静脉滴注阿奇霉素致不良反应,寻找阿奇霉素不良反应发生的规律以及表现,在临床应用中注意观察,避免发生不良反应。方法:选择2010年10月～2011年12月来我科采用静脉滴注阿奇霉素的患者150例,随机分为治疗组患者75例,对照组患者75例,治疗组患者采用减慢速度滴入阿奇霉素,对照组患者采用标准速度滴入阿奇霉素。观察两组患者出现不良反应的情况。结果:通过观察,治疗组患者出现的胃肠道反应、局部反应的发生率明显低于对照组,差异具有统计学意义(P<0.01),皮肤反应以及其他出现的不良反应的发生率无明显差异(P>0.01)。结论:在临床使用阿奇霉素需要注意用量及滴入速度,以保证患者使用药物的安全性。     

58例静脉输液反应发生的相关因素调查分析

目的：分析58例发生静脉输液反应的原因,提高静脉输液质量,减少静脉输液反应的发生。方法对本院近2年来发生的58例静脉输液反应从致热源、细菌、药物因素、输液器具、季节、患者年龄、环境、消毒剂浓度等方面进行分析。结果对静脉输液发生反应的药液进行热源检测,共有5例阳性;血培养7例阳性;药液细菌培养2例阳性;同一批号未开封药液细菌培养无细菌生长;输液器及头皮针细菌培养和热源检测全部阴性;引起静脉输液反应发生的药物以中药制剂、大分子物质、血液制品及含钾离子的药物为主;夏季为高发季节;发生率高的为老年人。结论发生静脉输液反应的因素是复杂的,它直接影响患者的治疗效果和生命安全,应针对影响因素采取有效地预防措施,有效降低静脉输液反应的发生。     

老年患者静脉输液的护理

目的 探讨老年患者静脉输液的护理方法. 方法 205例静脉输液治疗的老年患者随机分为两组：对照组105例,观察组100例.对照组采用常规静脉输液方法,输液过程中按常规每半小时巡视一次;观察组采取＂无痛穿刺安全输液＂方法,比较两种护理方法对静脉输液的影响. 结果 观察组一次性穿刺成功率为98%,高于对照组的88%（χ^2=8.14,P＜0.05）;观察组不良事件的发生率低于对照组（均P＜0.05）. 结论 采用＂无痛穿刺安全输液＂方法可以提高老年患者静脉输液护理质量.     

Effect of injection routes on pharmacokinetics and lactone/carboxylate equilibrium of 9-Nitrocamptothecin in rats

Pharmacokinetics and lactone/carboxylate equilibrium of 9-Nitrocamptothecin (9-NC) were compared after intravenous (i.v.) and intramuscular (i.m.) injection at a dose of 1.5 mg/kg 9-NC solution. The concentrations of three different forms of 9-NC, namely lactone, carboxylate and total 9-NC, were measured by HPLC analysis. Injection routes were demonstrated to have significant effect on pharmacokinetics of 9-NC. Compared with i.v. injection route, mean residence time (MRT) of 9-NC three forms was significantly prolonged following i.m. route (p < 0.05). The AUC_0–∞ ratios of i.m. to i.v. route were calculated to be 102 ± 43%, 273 ± 221% and 150 ± 62% for lactone, carboxylate and total 9-NC, respectively. Compared with i.v. injection route, although AUC_0–∞ was barely changed, MRT of lactone 9-NC was dramatically prolonged 4.5-fold after i.m. injection, which may account for the reported improved antitumor efficacy. However, the results of the present study also demonstrated that i.m. injection route increased both AUC_0–∞ and MRT of carboxylate 9-NC more significantly. Since the carboxylate form of CPT analogs including 9-NC is associated with their unwanted toxicity, i.m. injection route might lead to severe toxicity compared with i.v. route. Lactone/carboxylate equilibrium was also significantly influenced by injection routes. Based on the AUC_0–∞ measurements, the lactone 9-NC constituted 50 ± 8% and 32 ± 7% of circulating total 9-NC after i.v. or i.m. administration, respectively (p < 0.01).     

静脉输注化疗药物的风险管理效果观察

目的 对静脉输注化疗药物进行风险管理,并观察管理的效果.方法 分析静脉输注化疗药物存在的风险,制订强化护士风险意识、加强专业知识学习和专业技能训练、改进静脉穿刺方法、强化化疗巡视工作等措施,并且比较实施风险管理前后的护理差错、化疗发生外渗、静脉炎、局部组织坏死病例数量,并且对化疗患者的护理进行满意度调查.结果 风险管理实施后,护理差错、化疗药物外渗、静脉炎、局部组织坏死发生率明显较实施风险管理实施前显著减少,并且差异有统计学意义（P 〈 0.05）;在实施风险管理后,患者对护理工作的满意度较实施风险管理前显著增加,并且差异有统计学意义（P 〈 0.05）.结论 风险管理提高了静脉输注化疗药物的护理质量,提高了患者对护理的满意程度.     

某院住院病人抗菌药物静脉滴注情况调查分析

目的 调查该院住院病人静脉滴注抗菌药物的给药间隔、滴注时间和序贯滴注情况,分析其中存在的问题及原因,提出解决方法.方法 选取该院部分科室静脉滴注抗菌药物共532例护理执行单,对其给药间隔、滴注时间和序贯滴注情况进行追踪调查.结果 给药间隔合格率37.06%,滴注时间合格率81.90%,序贯滴注的合格率86.80%.结论 该院住院病人静脉滴注抗菌药物在给药间隔、滴注时间和序贯滴注方面存在不合理现象.可通过加强护理人员对抗菌药物基本知识的培训,在高峰时间合理安排护理人员和优化配置中心的工作方式,加强病人的用药宣教等方法,达到严格遵守抗菌药物的给药间隔和滴注时间,避免配伍禁忌的目的.     

Human dolasetron pharmacokinetics: I. Disposition following single-dose intravenous administration to normal male subjects.

Dolasetron is a 5-hydroxytryptamine antagonist active at type III receptors; it is presently undergoing clinical evaluation for the reduction/prevention of cancer chemotherapy-induced nausea and vomiting. Following intravenous administration to healthy male subjects of doses ranging from 0.6 to 5 mg kg-1, dolasetron disappeared extremely rapidly from plasma; concentrations were generally measurable for only 2-4 h. Less than 1 per cent of the dose was excreted intact in urine. A major plasma metabolite, reduced dolasetron, peaked rapidly at approximately 0.625 h (median). Its median terminal disposition half-life was 7.56 h; median values for fraction of dose excreted in urine and renal clearance were 31.0 per cent and 2.68 ml min-1 kg-1, respectively. Over the dose-range covered, pharmacokinetics of both dolasetron and reduced metabolite appeared to be independent of dose. The median ratio of the areas under the plasma concentration-time curves for metabolite relative to dolasetron was 11.9. As a result of its activity and significant plasma concentrations, reduced dolasetron may play a significant role in pharmacodynamic activity.     

Effect of duration of lidocaine infusion and route of cimetidine administration on lidocaine pharmacokinetics

The effects of the duration of lidocaine infusion and the route of cimetidine administration on lidocaine pharmacokinetics were evaluated in a randomized, three-phase crossover study of six healthy men. Lidocaine hydrochloride 100 mg was administered intravenously over two minutes, and plasma lidocaine concentrations were determined before treatment and at various intervals for three hours. Immediately after the three-hour sample was obtained, a second 100-mg dose of lidocaine hydrochloride was given, followed by a 21-hour constant infusion at a rate of 2 mg/min. Plasma lidocaine concentrations were determined at various intervals during the infusion and for eight hours afterward. Urine was collected during the last five hours of the infusion and assayed for lidocaine, monoethylglycinexylidide (MEGX), and glycinexylidide (GX). The following treatments were administered to each subject in a crossover manner: a placebo tablet every six hours, beginning two days before lidocaine administration; cimetidine 300 mg orally every six hours, beginning two days before lidocaine administration; and cimetidine hydrochloride 300 mg i.v. every six hours, beginning one hour before lidocaine administration. Each medication was given until the lidocaine infusion was discontinued. Subjects fasted and remained supine throughout each treatment period. Oral cimetidine increased the area under the concentration-time curve for lidocaine by 14.7% and increased the elimination half-life of lidocaine; i.v. cimetidine did not have a significant effect on lidocaine disposition. Lidocaine clearance was 34% lower under steady-state than single-dose conditions, but the effects of cimetidine on lidocaine disposition were similar under both conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of benzydamine after intravenous, oral, and topical doses to human subjects

The pharmacokinetics of the anti-inflammatory drug benzydamine were determined after intravenous infusion of 5 mg to six healthy male subjects. Benzydamine was characterized as a drug of relatively low systemic clearance (ca. 160 ml min-1) but high volume of distribution (ca. 1101); the apparent terminal half-life in plasma was ca. 8 h. Benzydamine was well absorbed after oral administration, as indicated by a mean systemic availability of 87 per cent. However, absorption of the drug was low (less than 10 per cent of the dose) after its use by male subjects as a mouthwash, or after its application to female subjects as dermal cream and vaginal douche preparations. The data suggest that benzydamine is generally not well absorbed through the skin and non-specialized mucosae, thereby limiting unrequired systemic exposure to this drug when it is used by these routes.