Pharmacokinetics of hexobarbital in man after intravenous infusion

The plasma levels of hexobarbital in humans were determined during and after a 30-min or 60-min zero-order intravenous infusion. Hexobarbital kinetics could be described by conceiving the body to exhibit two compartments. The plasma concentrations were fitted to the postinfusion equation and the parameters intrinsic to the two- compartment open model were estimated. The elimination half-life varied considerably among the 14 individuals (160–441 min), which could mainly be explained by the greatly varying metabolic clearance of the compound (123–360 ml /min). The apparent volume of distribution per kilogram of body weight was relatively constant (1.10±0.12 liters/kg).This work was supported in part by a grant from the Netherlands Foundation for Medical Research FUNGO.     

Pharmacokinetics of propylthiouracil in man after intravenous infusion

The kinetics of propylthiouracil in man was evaluated in four subjects after intravenous infusion at different infusion rates. Significant correlation among the rate of infusion, steadystate plasma levels, and AUC sustained the assumption of a doseindependent kinetics. The total body clearance and the elimination halflife evaluated after cessation of the infusion were in close agreement with values obtained in a previous study after intravenous bolus injection. The total volume of distribution was larger after infusion than found in the singleinjection studies. Data obtained from the infusions made it possible to evaluate the a phase indirectly.This work was supported by Grant 512-4121 from the Danish Medical Research Council, Copenhagen.     

Pharmacokinetics and dosage of digoxin in neonates and infants

Summary As a therapeutic principle, a disease should be treated with the lowest effective dose of a drug. Accumulating information indicates that satisfactory contractile response of the myocardium is produced in young paediatric patients by doses of digoxin below existing recommendations. In addition, toxicity appears to be more frequent in neonates and infants treated with digoxin than previously thought. Therefore, dose calculations have been performed, based on pharmacokinetic parameters, with the aim of reaching and maintaining an average serum concentration of the glycoside of 2 nmol/l. This level is common in infants (>1 month of age) during digoxin maintenance therapy and its adequacy is well supported by experience from adult cardiac patients.The calculations show that although current dosage schedules maintain the desired digoxin serum level in infants, they are often excessive for digitalization purposes. In neonates, the prevailing schemes do not sufficiently consider the immature state of the eliminating organs. Overdigitalization could therefore easily occur and continue in these patients, particularly in the premature newborns. This is in agreement with toxicity reports in the literature. The calculated doses should be less hazardous by being better adapted to the eliminating capacity of the various paediatric age-groups.Presented at the International Workshop on Perinatal and Pediatric Aspects of Clinical Pharmacology, Heidelberg, Federal Republic of Germany, 27–29 February 1980     

Determination of pharmacokinetic parameters of vitamin K1 in rats after an intravenous infusion

Pharmacokinetic parameters of vitamin K1 have a large range of values in different literature. The aim of this study was to determine the pharmacokinetic parameters of vitamin K1 following post-constant speed intravenous infusion (PCSII) to provide rational pharmacokinetic parameters of vitamin K1 and compare these with results of noncompartmental analysis following intravenous injection (IV). After 15 hours intravenous infusion of vitamin K1 in rats, the logarithmic concentration–time curve of vitamin K1 was fit to a linear equation following PCSII (R² = 0.9599 ± 0.0096). Then, half-time (T_1/2), apparent volume of distribution (V_d), and clearance rate (CL) were estimated successively. T_1/2 of vitamin K1 was 4.07 ± 0.41 hour, CL was 89.47 ± 3.60 mL/h, and V_d was 525.38 ± 54.45 mL in rats following PCSII. There was no significant difference in pharmacokinetic parameters of vitamin K1 among different sampling times. For noncompartmental analysis, T_1/2 and mean residence time (MRT_INF) for a sampling duration of 6h were shorter than those of 12 hours or 24 hours sampling duration following IV (P < .05, P < .01). In addition, T_1/2 of vitamin K1 was obviously different from MRT-equated half-time (T_{1/2, MRT})(P < .05). V_d and CL of vitamin K1 following PCSII were larger than those following IV based on noncompartmental analysis (P < .01). The results demonstrated that drug distribution in the body was balanced and the Napierian logarithmic concentration–time curve of vitamin K1 fit to a linear equation following PCSII. Vitamin K1 has a long T_1/2 and a relatively large V_d following PCSII.     

Pharmacokinetics of lansoprazole and its main metabolites after single intravenous doses in healthy Chinese subjects

1. The aim of the study was to evaluate the pharmacokinetics (PK) of lansoprazole (LPZ) and its main metabolites 5′-hydroxy lansoprazole (HLPZ) and lansoprazole sulphone (LPZS) after single intravenous (i.v.) doses of LPZ in healthy Chinese subjects, and the relationship between the cytochrome P450 (CYP) 2C19 phenotypes and the plasma concentrations of LPZS at the time-points in the elimination phase of LPZ.

2. Twelve subjects were given lansoprazole by i.v. infusion. Blood samples were collected at designated time points up to 24 h. Plasma concentrations of LPZ, HLPZ and LPZS were quantified by a selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method.

3. After single i.v. doses of 15, 30 and 60 mg LPZ, C_max and area under the plasma concentration-time curve (AUC_0-t) of LPZ were 725 ± 151, 1480 ± 190, 3130 ± 480 µg·L^?1 and 1690 ± 1210, 3630 ± 2530, 8080 ± 4550 µg·h·L^?1, respectively. LPZ was generally well tolerated in healthy Chinese subjects, and displayed linear PK in the range of 15–60 mg.

4. There were significant differences in the elimination of LPZ and the formation of LPZS between the single CYP2C19 poor metabolizer (PM) and the CYP2C19 extensive metabolizers (EM). The concentration of LPZS at the time-points in the elimination phase of LPZ could be monitored for CYP2C19 phenotyping. As a probe drug for CYP2C19 phenotyping, LPZ for injection might be more suitable than LPZ oral formulations.

     

高效液相色谱法测定奥硝唑的血药浓度及其人体药动学研究

目的:建立奥硝唑血浆浓度测定的反相高效液相色谱法,并用此法研究奥硝唑人体药动学.方法:采用Hypersil ODS色谱柱(250mm×4.6mm,10μm);以甲醇-0.01mol·L-1磷酸二氢钠(40∶60)为流动相,流速为1mL·min-1,检测波长318nm,甲硝唑作内标.结果:奥硝唑在0.5～32.0μg·mL-1浓度范围内呈线性,r=0.998 8.最低定量浓度0.5μg·mL-1.低、中、高浓度(1.0,8.0,32.0μg·mL-1)的方法回收率分别为86.2%,97.2%,96.8%;萃取回收率分别为73.8%,90.8%,92.9%,日内RSD<8%,日间RSD<11%.药动学研究表示,口服奥硝唑胶囊与片剂的药-时曲线均符合一级吸收、一级消除的一房室模型.结论:该法准确可靠,操作简便,适用于临床药动学研究及血药浓度监测.     

Pharmacokinetics of furosemide in neonates

Summary The pharmacokinetics of furosemide was evaluated in 12 newborns who received the drug transplacentally, and in 21 neonates who received it directly for therapeutic reasons. In the first group, the apparent plasma half-lives ranged from 96 to 6.8 h with a significant inverse relationship (p<0.01) between the gestational age and the elimination rate. In two cases a clear effect on diuresis was also observed. In the neonates receiving the drug i.v. for therapeutic reasons, the elimination kinetics appeared to follow a two-compartment open model, with a significant difference in the therminal plasma half-life between premature (26.8±12.2 h) and full-term newborns (13.4±8.6 h). In this group no relationship was observed between elimination rate and either gestational or conceptional age. In the case of repeated administration, an increase in plasma clearance and reduction in t_1/2 β was noticed.     

Pharmacokinetics of rec-hirudin in healthy volunteers after intravenous administration

The pharmacokinetics of recombinant hirudin (rec-hirudin, Ciba-Geigy, CGP 39 393) in healthy volunteers after iv administration was investigated on the basis of the data from five different studies. A total of 77 plasma profiles following a single iv bolus dose of either 0.1, 0.3, 0.5, or 1 mg/kg of rec-hirudin was used for the evaulation. Plasma concentrations and especially AUC were proportional to the dose. Kinetics of rec-hirudin after a bolus iv injection were best described by a three-compartment open model. Mean apparent terminal half-life was 2.8 hr and the total clearance 0.138 L/hr per kg.     

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.     

静脉滴注盐酸卡屈沙星注射液的健康人体药动学研究

目的:研究静脉滴注盐酸卡屈沙星葡萄糖注射液在健康人体内的药动学。方法:20名健康成年志愿者随机分成两组,每组10人,男女各半,分别静滴盐酸卡屈沙星葡萄糖注射液0.3和0.4 g后,采用HPLC法测定血药浓度,使用DAS软件求出药动学参数。结果:两组的最大血药浓度(Cmax)分别为(5.2±0.6)和(7.3±1.7)μg.mL-1;消除半衰期(t1/2z)分别为(6.4±1.4)和(6.3±1.4)h;表观分布容积(Vz)分别为(90.9±22.7)和(83.4±21.3)L;清除率(CL)分别为(9.8±1.6)和(9.3±1.7)L.h-1;药时曲线下面积(AUC0～24)分别为(30.5±5.2)和(42.2±8.2)μg.h.mL-1。结论:t1/2z,Vz和CL经统计学检验,两组间无显著性差异,Cmax和AUC0～24与给药剂量呈正比。     

Pharmacokinetics of theophylline in patients following short-term intravenous infusion

Summary Serum theophylline concentrations after intravenous administration of a new short-term infusion (Euphyllin^® Kurzzeitinfusion) were measured in 50 out-patients with chronic obstructive airways disease (COAD). An intravenous infusion of theophylline ethylenediamine 480 mg (corresponding to approximately 350 mg anhydrous theophylline) in 50 ml isotonic solution was given in 20 min. Blood samples were taken beforehand and 25 to 30 min and 1, 3 and 6 h after starting the infusion. 86% of the patients had a one-hour serum level in the therapeutic range of 8–20 mg/l, and 2 h later, this was true of 64% of the patients. The short-term infusion was well tolerated, even in cases with unknown high pre-infusion serum levels. Pertinent pharmacokinetic parameters were determined, such as total body clearance, apparent volume of distribution, and half-life of elimination. Geometric mean and 95%-confidence limits, derived from the log-normal distribution of these parameters, were: Cl=0.044 (0.018–0.109) l/h/kg ideal body weight, V_d=0.451 (0.258–0.789) l/kg ideal body weight, and t_1/2(el)=7.1 (2.6–19.1) h.     

Pharmacokinetics of dexamethasone in premature neonates

Objective: Dexamethasone is frequently used in premature neonates with bronchopulmonary dysplasia, however little is known about its disposition in this population. Methods: We evaluated the pharmacokinetics of dexamethasone in 9 premature neonates with a mean gestational age of 27.3 weeks and a postnatal age of 21.8 days. Results: There was a strong relationship between clearance (4.96 ml·min^–1·kg^–1) and gestational age (r=0.884). Pharmacokinetic parameters were grouped based on a gestational age of less than 27 weeks (Group I) and greater than 27 weeks (Group II). Mean clearance in group I and group II was 1.69 and 7.57 ml·min^–1·kg^–1, respectively. Mean distribution volume in group I and II was 1.26 and 2.19 l·kg^–1, respectively. No significant relationships were noted between the disposition of dexamethasone and ventilator requirements or adverse effects. Conclusion: The pharmacokinetics of dexamethasone in premature neonates was related to gestational age.     

Acute hypotensive action of clonidine after intravenous infusion in hypertensive emergencies

Summary Clonidine was administered by intravenous infusion to 12 patients classified as having exaggerated arterial hypertension, their systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures were significantly reduced from the third min. The maximal percentage reduction (Mean±SEM) reached 30.1±3.1% (SAP) and 24.7±2.9% (DAP) after 30 to 110 min of infusion. Initially there were transitory initial increases in SAP (3 patients) and DAP (1 patient). The increases in blood pressure were related to low body surface area (BSA). The dose of clonidine per m² BSA able to reduce by 10% either SAP or DAP (active dose-10), and the dose able to reduce SAP or DAP by 10 mmHg in one minute (systolic or diastolic clonidine unit) were calculated, providing indices for detecting clonidine responsiveness in patients with exaggerated hypertension. This method is advantageous when using clonidine intravenously because it diminishes the risk of overdosage.     

某三甲医院实施静脉输液专项检查管理成效分析

目的：探讨安徽省卫计委开展静脉输液专项检查前后医院门急诊静脉输液管理成效评价。方法：采用回顾性分析方法,对某三甲医院2014年（检查前）和2015年（检查后）门急诊静脉输液相关数据进行统计分析。结果：开展静脉输液专项检查后,急诊患者静脉输液率、门急诊患者静脉输液处方比例与同期相比均显著下降（P<0.05）,差异有统计学意义。结论：安徽省卫计委开展静脉输液专项检查有利于规范医疗机构门急诊静脉输液,显著提高医疗机构门急诊静脉输液管理质量。     

抗真菌药物在新生儿和婴儿体内的药动学

目前大多数抗真菌药物的药动学数据来自成人,尚未建立不同年龄组儿童给药剂量的标准,且并非所有抗真菌药物都被批准用于新生儿和婴儿真菌感染的预防和治疗。然而新生儿和婴儿药动学特点与成人不同,且药动学参数随生长发育而变化。常用抗真菌药物(多烯大环内酯类、氟化嘧啶类、唑类和棘白菌素类)在新生儿和婴儿体内的吸收、分布、代谢和排泄过程具有较大的个体差异,也不同于其他年龄段儿童。目前抗真菌药物在新生儿和婴儿体内的药动学研究大多限于案例报道,应进一步开展抗真菌药物在新生儿和婴儿体内的药动学和药效学研究。     

Critical parameters in drug delivery by intravenous infusion

Introduction: Intravenous infusion is commonly used to deliver medications and fluids to patients. The duration of an infusion is short (hours) in the operating room where intravenous agents are infused to anesthetize patients and to manage circulation. Critically ill patients often receive infusions for days. Infusion technology has become increasingly sophisticated and complex. The technical advances broaden the clinical application of intravenous infusion methodology and provide safety features.

Areas covered: This article provides an historical overview of intravenous infusion and discusses components of infusion systems. A section describes configuration of components to meet clinical needs. The article describes physical properties of infusion systems, emphasizing how critical parameters of resistance to flow, infusion pump performance and interactions between fluid flows and the dead volume influence medication and fluid delivery. The authors emphasize the use of infusions in the intensive care and operating room environments, although the general principles apply to other clinical settings.

Expert opinion: Intravenous infusion systems contribute significantly to clinical care, but in a deceptively simple way. Several critical parameters combine to influence the performance of an infusion system, with a number of pitfalls potentially confounding utility of the technology. Safe and effective clinical application of intravenous infusion technology depends on an appreciation of this complexity which impacts the performance of infusion systems.     

静脉输液技术发展及安全管理

随着医学的不断进步,静脉输液工具及穿刺方式发生了很大的改变,为提高临床输液护理的质量、提高静脉输液安全以及降低静脉输液中的相关并发症,文章对遵循静脉治疗评估流程,严格执行输液实践标准,主动采取职业防护措施,降低输液治疗中的风险进行了全面的阐述。     

Pharmacokinetics of intravenous and oral L-arginine in normal volunteers

AIMS: Recent studies in patients with cardiovascular diseases suggest potential for the use of orally administered L-arginine, the precursor of nitric oxide, as a therapeutic agent. This crossover study was designed to examine the pharmacokinetics of single i.v. and oral doses of L-arginine in healthy volunteers (n = 10). METHODS: A preliminary control study (n = 12) was performed to assess the variation in plasma L-arginine concentrations when ingesting a normal diet. The observed variation was taken into account when interpreting the pharmacokinetic data obtained after exogenous administration. RESULTS: The mean baseline plasma concentration of L-arginine in the control study was 15.1+/-2.6 microg ml(-1). After intravenous administration (30 g over 30 min), the plasma concentration reached 1390+/-596 microg ml(-1). The disappearance of l-arginine appeared biphasic, with an initial rapid disappearance due to concentration-dependent renal clearance followed by a slower fall in plasma concentrations due to nonrenal elimination. The peak concentration after oral administration (10 g) was 50.0+/-13.4 microg ml(-1), occurring 1 h after administration. Renal elimination was not observed after oral administration of this dose. The absolute bioavailability of a single oral 10 g dose of L-arginine is approximately 20%. CONCLUSIONS: This study provides basic knowledge of L-arginine pharmacokinetics in healthy humans. Intravenous and oral administrations show at minimum a biphasic pattern. Further studies will assess whether a similar profile is observed when the drug is administered to patients.