Population analysis of the non linear red blood cell partitioning and the concentration-effect relationship of draflazine following various infusion rates

Aims To investigate the impact of the specific red blood cell binding on the pharmacokinetics and pharmacodynamics of the nucleoside transport inhibitor draflazine after i.v. administration at various infusion rates. It was also aimed to relate the red blood cell (RBC) occupancy of draflazine to the ex vivo measured adenosine breakdown inhibition (ABI). Methods Draflazine was administered to healthy volunteers as a 15-min i.v. infusion of 0.25, 0.5, 1, 1.5 and 2.5 mg immediately followed by an infusion of the same dose over 1 h. Plasma and whole blood concentrations were measured up to 120 h post dose, and were related to the ex vivo measured ABI, serving as a pharmacodynamic endpoint. The capacity-limited specific binding of draflazine to the nucleoside transporter located on the erythrocytes was evaluated by a population approach. Results The estimate of the population parameter typical value (%CV) of the binding constant K_d and the maximal specific binding capacity (B_max ) was 0.385 (3.5) ng ml⁻¹ plasma and 158 (2.1) ng ml⁻¹ RBC, respectively. The non-specific binding was low. The specific binding to the erythrocytes was a source of non-linearity in the pharmacokinetics of draflazine. The total plasma clearance of draflazine slightly decreased with increasing doses, whereas the total clearance in whole blood increased with increasing doses. The sigmoidal E_max equation was used to relate the plasma and whole blood concentration of draflazine to the ex vivo determined ABI. In plasma, typical values (%CV) of E_max, IC₅₀ and Hill factor were 81.4 (1.9)%, 3.76 (9.3) ng ml⁻¹ and 1.06 (3.4), respectively. The relationship in whole blood was much steeper with population parameter typical values (%CV) of E_max, IC₅₀ and Hill factor of 88.2 (2.0)%, 65.7 (2.8) ng ml⁻¹ and 4.47 (5.5), respectively. The RBC occupancy of draflazine did not coincide with the ex vivo measured ABI. The observed relationship between RBC occupancy and ABI was not directly proportional but similar for all studied infusion schemes. Conclusions The findings of this study show that the occupancy of the nucleoside transporter by draflazine should be at least 90% in order to inhibit substantially adenosine breakdown in vivo. On the basis of these findings it is suggested that a 15 min infusion of 1 mg draflazine followed by an infusion of 1 mg h⁻¹ could be appropriate in patients undergoing a coronary artery bypass grafting.     

In-vitro red blood cell partitioning of doxycycline

Objective:

In-vitro red blood cell (RBC) partitioning of doxycycline was studied to determine whether doxycycline penetrates RBC and its concentration was assayed keeping in view its high lipophilicity.

Materials and Methods:

Standardization of doxycycline was performed in whole blood and plasma of cattle by microbiological assay using Bacillus subtillis ATCC 6633 as indicator organizm. Actual concentration of the drug was obtained by comparing zone inhibition with standard graph and the extent of partitioning was mathematically calculated.

Results:

The R² value of standard graph for doxycycline was 0.9934 and 0.9727 for plasma and whole blood, respectively. Overall, RBC partitioning of doxycycline was found to be 18.40 ± 1.70%.

Conclusions:

Overall RBC partitioning of doxycycline indicated low penetration into RBC. Plasma is the fluid suggested for pharmacokinetic evaluation of doxycycline.     

High-performance liquid chromatographic analysis, plasma protein binding and red blood cell partitioning of phenprobamate

A new high-performance liquid chromatographic procedure for the analysis of phenprobamate, a skeletal muscle relaxant in biologic fluids was developed. The method used a C18 reverse phase column, a mobile phase of methanol/acetonitrile/water (33:15:52), and UV detection at 215 nm. The assay procedure was applied to the determination of phenprobamate binding to rat and human plasma proteins using the equilibrium dialysis method. In addition, the red blood cell/plasma partitioning was determined in the whole blood of rats and humans. Phenprobamate exhibited a moderate binding to plasma proteins of rat (74.3 +/- 2.2 per cent) and human (80.5 +/- 1.1 per cent). The protein binding was concentration-independent in the range of 10 to 80 micrograms ml-1. Phenprobamate binding to plasma proteins was also determined in the presence of 10 micrograms ml-1 acetaminophen. The protein binding of phenprobamate was not significantly altered by acetaminophen (74.4 +/- 0.6 per cent for rat plasma; 75.7 +/- 1.6 per cent for human plasma). The distribution ratios of phenprobamate between the red blood cells and plasma were greater than unity, 1.86 and 1.59 in rat and human, respectively, indicating a preferential partitioning of the drug in the red blood cells.     

Normal range of human red blood cell acetylcholinesterase activity

The normal range of human erythrocyte acetylcholinesterase (RBC-AChE) activity is important when monitoring exposure to pesticides and chemical warfare agents. A modification of Michel’s method measured RBC-AChE activities from 991 individuals (818 males and 173 females) presumably unexposed to nerve agents. Median age was 42 (range, 18–76) years. RBC-AChE (mean ± SD) was 0.74?±?0.06 delta pH units/hour. Multivariate linear regression showed an association with age (slope +0.0008 delta pH units/hour for each year; P?<?0.001) unlikely to be clinically significant. The findings represent the largest study of human RBC-AChE to date providing measures of central tendency and variation.     

八珍汤对红细胞免疫功能作用的实验研究

目的：探讨八珍汤对红细胞免疫功能的作用。方法：观察小白鼠随年龄增长其红细胞免疫功能的变化及古方八珍汤对老龄小白鼠红细胞免疫功能的影响。结果：①老龄小白鼠的红细胞c3b受体花环率（RBC．C3bRR）显著低于低龄者（P＜0．01）,而老龄小白鼠的循环免疫复合物花环率（RBC．ICRR）则明显高于低龄者（P＜0．01）。②老龄小白鼠服用八珍汤（20g/kg）后的RBC．C3bRR明显高于服药前水平（P＜0．01）,而服药后的RBC．ICRR则明显低于药前水平（P＜0．01）。结论：①随着年龄的增长,红细胞免疫功能呈明显低下状态,②古方八珍汤具有一定增强老龄机体红细胞免疫功能而起到抗衰老的作用。     

红细胞体积分布宽度在贫血诊断中的临床意义

目的：探讨贫血患者红细胞体积分布宽度的变化及其临床意义。方法：应用sysmex F-820血细胞分析仪测定164例贫血患者红细胞体积分布宽度变异系（RDW-CV）。结果：MCV↓RDW↑缺铁性贫血、MCV↑RDW↑巨幼红细胞性贫血、MCV和RDW异常,急性再生障碍性贫血、MCV↑RDW,慢性再生障碍性贫血、MCV↑RDW↑溶血性贫血、MCV、RDW↑铁粒幼细胞性贫血、MCV↓RDW,单纯小细胞性贫血。结论：RDW指标的改变对贫血的分类及缺铁性贫血的诊断有较好的敏感性和特异性。     

尿液潜血检验中尿液分析仪、显微镜红细胞计数的应用效果探究

目的 分析尿液潜血检验中尿液分析仪、显微镜红细胞计数的应用效果.方法 90份进行尿液检验分析患者的尿液标本,分别进行显微镜红细胞计数检验与尿液分析仪检验,观察两种方法的检验结果 ,以显微镜红细胞计数检验结果为金标准,分析尿液分析仪检验的敏感度、特异度、误诊率、漏诊率.结果显微镜红细胞计数检验阳性20例,阴性70例,阳性...     

Nonlinear relationship between plasma and red blood cell pharmacokinetics of chlorthalidone in man

Plasma concentrations, red blood cell concentrations, and urinary excretion of chlorthalidone were measured after oral administration of single doses of 100 or 200 mg to ten human subjects. The decay of red blood cell concentrations showed a much longer elimination half-life than the terminal plasma decay curve. The in vitrodistribution of chlorthalidone between plasma and erythrocytes was similar to the in vivodistribution curve obtained from patients who were in a steady-state concentration range. A pharmacokinetic model was developed including nonlinear binding of chlorthalidone by the red blood cells, which in detail accounted for the observed time courses of drug in plasma and erythrocytes simultaneously.This work was supported in part by a grant from the Netherlands Foundation for Medical Research (FUNGO).     

Minor red blood cell antigen phenotyping of athletes sampled in international competitions

Blood transfusion is performed by cheating athletes to rapidly increase oxygen delivery to exercise muscles and enhance their performance. This method is banned by the World Anti-doping Agency (WADA). Heterologous or allogenic blood transfusion happens when blood from a different person is transfused. The method used to detect this type of doping is based on flow cytometry, by identifying variations in blood group minor antigens present on the red blood cells' surface. Transfusion practices have regained interest since the introduction of human recombinant erythropoietin detection method. It has been reported that the number of occurrences of two athletes sharing an identical phenotype in the same sport was five times higher than the theoretical populational probability. The present work describes the prevalence of 10 erythrocytes surface antigens in a population of 261 athletes from all five continents. The matching phenotype per sport is also described.     

洗涤红细胞的临床应用

目的 探讨洗涤红细胞( W RC ) 的临床应用效果。方法 应用洗涤红细胞治疗 50例贫血病人,另一同病种病人 38例输全血 ( 剂量与洗涤红细胞相当)治疗后,比较 2组红细胞 ( ) RBC 、血红蛋白 H GB) ( 、红细胞压积 ( )的结果变 H CT化。结果 应用洗涤红细胞治疗后的 50例贫血病人其 RBC、H CB、H CT 水平明显高于输全血治疗后的 38例贫血病人 (P<0.01) 。结论 应用洗涤红细胞治疗贫血病人,尤其是治疗自身免疫性溶血性贫血病人,疗效确切。     

缺铁性贫血的红细胞平均指数检测分析

目的探讨缺铁性贫血（IDA）检测红细胞平均指数的意义和价值。方法选取200例研究对象,分为缺铁性贫血组、正常组各100例,各组患者均行平均红细胞体积（MCV）、平均红细胞血红蛋白含量（MCH）、平均红细胞血红蛋白浓度（MCHC）联合化验检测,对比分析各组化验结果。结果缺铁性贫血组的MCV、MCH、MCHC均显著低于正常组,P均〈0．01。结论MCV、MCH、MCHC联合检测对缺铁性贫血具有极大诊断价值．可做为IDA筛选实验指标。     

疫苗激活红细胞增强白细胞释放IL-8的实验研究

目的:探讨疫苗对红细胞调控白细胞免疫反应的激活作用。方法:将卡介苗(1mg/mL)和/或癌细胞瘤苗(5×106个细胞/mL)或酵母菌苗(5×108个细胞/mL)或生理盐水(对照组)0.2mL,加到枸橼酸抗凝的全血细胞悬液(或白细胞悬液)0.2mL和血浆0.3mL中,37℃水浴1h,用酶联免疫法测定反应液中IL-8含量。结果:各种疫苗加至全血细胞和血浆组中IL-8激活指数为(2.56±1.32),明显高于各种疫苗加至白细胞和血浆组的IL-8激活指数(0.70±0.75),P<0.05。结论:在血浆的参与下,各种疫苗可激活红细胞增强白细胞产生IL-8。本研究为疫苗的制备和疫苗免疫活性的测定提供了有用的新方法。     

高原红细胞增多症16例围术期麻醉管理体会

16例高原红细胞增多症 (简称高红症 )病人 ,在围术期我们针对该类患者其血液成分 ,微循环 ,血液流变学等方面发生的一系列生理或 /和病理性改变。采取了血液稀释和自体输血等相应的对策 ,取得了较好的手术麻醉效果 ,大大降低了高红症病人手术麻醉的危险性     

免疫调节药激活红细胞天然免疫反应主干道研究

目的测定生物免疫调节药(BIRL)对红细胞天然免疫反应主干道的激活作用.方法癌细胞(5×106·mL-1)和(或)生物免疫调节药(或0.9%氯化钠溶液)0.2 mL或0.1 mL加到新鲜枸橼酸抗凝血的全血细胞悬液0.2 mL或白细胞悬液0.2 mL和血浆0.3 mL(或0.9%氯化钠溶液0.3 mL)中,37 ℃温育1 h后观察结果,主要指标是白细胞介素-8(IL-8)(免疫酶联测定法).结果发现癌细胞或生物免疫调节药可激活血液免疫反应,但癌细胞和生物免疫调节药加到全血细胞组IL-8激活指数(1.82±0.69)明显高于癌细胞和生物免疫调节药加到白细胞组的IL-8激活指数(0.37±0.63),P<0.01,癌细胞加生物免疫调节药组IL-8激活指数(1.28±0.833)高于癌细胞未加生物免疫调节药组IL-8激活指数(0.867±0.507).结论结果表明在血液免疫反应中存在红细胞主干道路线图,生物免疫调节药能增强红细胞天然免疫反应主干道抗肿瘤免疫功能.     

尿标本种类对尿红细胞位相检查的影响

目的探讨晨尿、随机尿、新鲜尿对尿红细胞位相检查诊断肾小球性血尿的影响。方法入选有血尿的患者108例,确诊为肾小球病变的62例,非。肾小球病变的46例。用相差显微镜观察晨尿、随机尿、新鲜尿标本中的红细胞形态。以尿红细胞〉8000个／ml,其中畸形红细胞〉70％;G1红细胞≥5％,作为肾小球性血尿的诊断标准,评估不同标本行尿红细胞位相检查的灵敏度、特异度和准确性。结果晨尿、随机尿、新鲜尿标本诊断肾小球疾病的灵敏度分别为72。6％、80．6％和87．1％,晨尿灵敏度低于新鲜尿标本（P〈0．05）;特异度分别为78．2％、89．1％和93．5％,晨尿特异度低于新鲜尿标本（P〈0．05）;准确性分别为75％,84．3％和89．8％。结论新鲜尿标本在鉴别血尿来源方面更具优势,行尿红细胞位相检查应尽可能采集这种标本。     

人红细胞保护蛋白对羟基自由基的清除作用

目的研究人红细胞保护蛋白 (HRPRP)在体外对羟基自由基 (·OH)的清除作用并探讨其抗氧化机制。方法可见光照射试管内N 羟基 2 硫代吡啶酮产生·OH ,用脱氧核糖作检测分子 ,分光光度法测定N 羟基 2 硫代吡啶酮随光照时间产生·OH的量。在反应体系中加入不同浓度的铜锌超氧化物歧化酶 (Cu ,Zn SOD)、HRPRP及二硫苏糖醇 (DTT)活化HRPRP ,观察它们对N 羟基 2 硫代吡啶酮产生的·OH的清除作用。结果Cu ,Zn SOD和HRPRP对·OH的清除率无显著性差异 (P >0 .0 5 ) ,DTT活化的HRPRP对·OH的清除率显著大于Cu ,Zn SOD(P <0 .0 1)及未活化HRPRP(P <0 .0 1)。结论证实HRPRP在巯基还原剂提供还原当量 ,暴露其自身活性位点时具有高效而特异的清除·OH的能力 ,提示HRPRP清除·OH可能是重要的抗氧化机制之一。     

肾移植后环孢素A血药浓度与红细胞及血红蛋白的相关性分析

目的 探讨肾移植受者术后ＣｓＡ血药浓度与ＢＲＣ数及ＨＧＣ含量的相关性。方法 应用ＦＰＩＡ法测定４０例肾移植受者术后ＣｓＡ血药浓度,分析术后不同时间ＲＢＣ数及ＨＧＢ含量对ＣｓＡ血药浓度的影响。结果 在术后早期ＣｓＡ用量基本不变的情况下,ＣｓＡ血药浓度与ＲＢＣ数及ＨＧＢ含量有显著正相关。结论 术后早期ＲＢＣ和ＨＧＢ可能是影响ＣｓＡ血药浓度的因素之一。