持续性不卧床式腹膜透析患者腹腔内使用万古霉素的治疗药物监测

目的:对持续性不卧床式腹膜透析患者腹腔内使用万古霉素进行监测,为万古霉素用药方案调整提供依据。方法:6名持续性不卧床式腹膜透析腹膜炎患者腹腔内使用万古霉素后,采集不同时间点的血浆和腹膜透析液样品,用高效液相色谱法测定血药浓度和腹膜透析液中药物浓度。结果:万古霉素加入腹膜透析液中给药的生物利用度为93.27%。给药后10h(第1次腹膜透析液放出来前)患者血药浓度约为21.71μg·mL-1,最低血药浓度(下次给药前)为11.39μg·mL-1;腹膜透析液中药物谷浓度为5.62μg·mL-1。结论:万古霉素加入腹膜透析液中给药,能够确保万古霉素有效吸收,且使腹腔局部保持有效的抑菌浓度,未造成万古霉素蓄积。     

环丙沙星在老年慢性阻塞性肺病患者多次给药的药动学研究

应用微生物法测定6名老年慢性阻塞性肺病患者多次po环丙沙星片后的血清药物浓度,药物体内过程符合一室模型,其主要药动学参数分别为:T_(1/2)=5.14±1.13h,Vc/F=6.6±4.2L╱kg,(C∞)max=2.73±1.02μg/ml;T_p~′=0.96±0.44h,测定方法平均回收率为101.6％。     

头孢三嗪的药物动力学及其与血管外室浓度的关系

第三代头孢菌素头孢三嗪(Ceftriaxone,Ⅰ)和头孢噻肟(Cefotaxime,Ⅱ)均具有较广的抗菌谱,但药代动力学表现有很大差别。实验显示,静注1g 药物后,Ⅱ血浓度达100 μg/ml,1 h 和2 h 血浓度分别迅速下降至15和5 μg/ml,t1/2β为1.1 h;而Ⅰ峰浓度达150～170μg/ml,2h 和12h 分别为100和35 μg/ml,24h 仍有10 μg/ml,t1/2β为8～9h。Wise 等比较了Ⅰ和Ⅱ的组织渗透性,给1 gⅡ后1 h,皮肤水泡中最高浓度为7μg/ml;给0.5g Ⅰ则在6h 达峰浓度32μg/ml,24h 仍有10μg/ml。作者测定了两种抗生素在血清和腹水的浓度,静注15mg/kg 时,Ⅰ血清峰浓度为177μg/ml,2 h 97μg/ml,24 h 16 μg/ml,平均t1/2β芦为13h,其腹水     

抽脂患者皮下注射利多卡因血清与唾液浓度的相关性及其药代动力学研究

本文利用高效液相色谱法对12名抽脂健康患者皮下注射利多卡因的血清、唾液及脂肪浓度进行了测定,探讨了血清与唾液中药物浓度的相关性,并比较了二者之间的药代动力学参数。患者的平均给药剂量为20mg/kg,单剂量给药。实验结果表明血清与唾液中药物浓度呈线性关系:r=0.8043(p<0.01),C_(血清)=0.3433C_(唾液)+0.2620(n=78).唾液与血清药物浓度比值为2.37±0.857(比值范围:1.02～4.09,n=78).测得血清及唾液药代动力学参数分别为:吸收速率常数(Ka)0.573±0.583h~(-1),0.478±0.270h~(-1);消除半衰期(t_(1/2)k)6.41±2.08h,5.68±1.76h;达峰时间(T_(max))6.63±1.46h,6.67±1.80h;峰浓度(C_(max))2.52±0.926μg/ml,6.31±2.30μg/ml.血清与唾液的动力学参数除峰浓度(C_(max))外,统计学上均无明显差异(P>0.05).患者被抽出脂肪的药物含量为给药总量的31.84%(20.69～47.90%).     

头孢唑肟栓剂的基础临床研究

头孢唑肟栓剂(CZX-S)是日本京都药品公司和藤泽药品公司共同开发的头孢抗生素栓剂.本品直肠给药吸收后可达到充分的有效治疗血浓度.高龄者4例一次给药CZX-S500mg,给药后30分钟的血清浓度平均值为0.93μg/ml,1小时为1.31μg/ml,6小时后为0.40μg/ml,半衰期为3.02小时,0～2小时的尿浓度为37.9μg/ml,2～4小时为86.8μg/ml,4～6     

复方磺胺甲恶唑分散片在正常人体内的药代动力学及相对生物利用度

本文采用HPLC法同时测定血浆中复方磺胺甲噁唑吐分散片中SMZ和TMP的浓度,采用HypersilODS柱,流动相为乙腈:醋酸钠(pH6.4 0.lmol/L)=22:78(V/V),检测波长230nm,流速为1.00ml/min.10名志愿受试者自身交叉口服Go-SMZ片和Co-SMZ分散片800mg,结果显示SMZ和TMP的Cmax分别为46.69±7.66μg/ml,44.61±6.37μg/ml和1.82±0.49μg/ml,1.63±0.43μg/ml;Tmax为3.41±1.59h,3.4±0.84h和1.48±0.83h,1.50±0.81h;AUC为761±l29.37μg.h/ml,761.79±145.6μg.h/ml和26.91±3.89μg.h/ml,26.96±4.7lμg.h/ml.分散片中SMZ和TMP相对于参比制剂的相对生物利用度分别为101.28±14.35%,101.26±15.76%.     

氯唑沙宗片的药动学及相对生物利用度

在10名健康志愿者进行了两种氯唑沙宗片的药动学比较.按交叉试验设计,Po给药,用高效液相色谱法测定氯唑沙宗的血药浓度,其药时曲线符合一室模型.待测片的药动学参数:C_(?)=12.30±3.74μg/ml,Td_(?)=1.13±0.23h,K=0.88±0.15h,T_(1/2)=0.81±0.14h,AUC_(0～(?)h)=31.49±10.60μg·h/ml.待测片的相对生物利用度为107.21%,与标准片具有生物等效性.     

人尿中苯丙哌林的比色测定法及其应用

本文利用苯丙哌林结构中活性亚甲基与显色剂(对-二甲氨基苯甲醛)酸性溶液呈粉红色专属性反应,建立了苯丙哌林尿液浓度的可见光比色测定法。其最低检测浓度为5μg/ml,平均回收率为100.9±4.0(%),相关系数r=0.9994,回归方程y=0.0107x-0.0339,日内误差CV(%)=2.60,日间误差CV(%)=4.23.6名健康志愿者口服苯丙哌林片剂100mg,尿药测定结果的1g△x/△t-t曲线出现前高型双峰现象,即服药后7h出现第一高峰,此时平均尿药排泄速度为1.90±0.15μg/h,30h出现第二高峰,此时其平均尿药排泄速度为1.61±0.09μg/h.     

家兔血浆丹皮酚浓度的测定

用分光光度法测定家兔血浆丹皮酚浓度,回归方程A=-1.518×10~(-8)+8.326×10~(-4)C,r=0.9997。平均回收率100.6±2.96％。用26mg丹皮酚花生油溶液,对2.5±05kg健康家兔肌肉注射给药,用该法测定给药后一定时间血浆丹皮酚的浓度。结果表明,肌肉注射给药30min后,丹皮酚吸收入血,2.5h到达吸收高峰,最大浓度为20.8±2.9μg/ml,8h后血浆丹皮酚基本消失。     

国产头孢克罗胶囊剂的人体相对生物利用度研究

目的：通过12名男性健康志愿者对国产头孢克罗胶囊进行药物动力学和相对生物利用度研究。方法：采用HPLC法测定血浆药物浓度,所有受试者随机交叉单剂量口服500mg国产或进口头孢克罗胶囊。结果：两种药品的药-时曲线符合一室开放模型,国产和进口头孢克罗胶囊的峰浓度Cmax为（16．45±3．03）和（16．72±3．83）μg／ml;达峰时间TMAX为（0．75±0．21）和（0．67±0．19）h;消除半衰期T1/2ke为（0．15±0．10）和（0．50±0．12）h,药-时曲线下面积AUC0－t为（19．58±1．85）和（19．45±2．49）h／（μg．ml）。结论：统计分析结果表明,国产与进口头孢克罗胶囊具有生物等效性,国产胶囊的相对生物利用度为（101．39±9．73）％。     

Passage of digoxin into cerebrospinal fluid in man

The passage of digoxin into the cerebrospinal fluid (CSF) was studied in 8 infants on maintenance therapy with digoxin, 11 adult patients on long-term digoxin therapy, and 15 patients, previously non-digitalized, who were given 0.5 mg digoxin orally 1 hr to 12 hrs prior to lumbar puncture. Digoxin in the serum and CSF was determined by radioimmunoassay. In the infants a mean serum concentration of 1.5 ng/ml (range 0.7-2.3 ng/ml) was found, and a simultaneous mean CSF concentration of 0.5 ng/ml (range 0.3-1.1 ng/ml). In the adults on long-term therapy, the corresponding figures were 1.1 ng/ml (range 0.5-2.2 ng/ml) and 0.3 ng/ml (range 0-0.6 ng/ml). Among the 15 patients given a single oral dose of digoxin, detectable CSF concentrations (0.2-0.3 ng/ml) were found in five, 1-12 hrs after the administration of the drug. In three paediatric patients with hydrocephalus (3 months-5 years) digoxin therapy was started as an attempt to decrease CSF production. In these patients, the production of CSF was reduced by 17, 25 and 30%, respectively.     

Peritoneal dialysis fluid concentrations of linezolid in the treatment of vancomycin-resistant Enterococcus faecium peritonitis

OBJECTIVE: To determine linezolid concentrations in peritoneal dialysis fluid after multiple oral doses of the drug in a 46-year-old man with vancomycin-resistant Enterococcus faecium peritonitis who was undergoing peritoneal dialysis. METHODS: After administration of oral linezolid 600 mg twice/day was started, peritoneal dialysis fluid was collected at the end of several 4- and 8-hour dwell times and submitted for analysis of linezolid concentration. Before linezolid therapy was begun, and immediately after several peritoneal dialysis exchanges, 30 ml of expended peritoneal dialysis fluid was collected in a sterile container and immediately frozen at -70 degrees C until analysis by high-performance liquid chromatography. RESULTS: Peritoneal dialysis concentrations of linezolid greater than 4 microg/ml were achieved after the first dose of linezolid and maintained after repeated doses. During the course of therapy, mean linezolid concentrations in peritoneal dialysis fluid tended to increase (mean 7.60 pg/ml, range 3.54-16.2 microg/ml). All assayed peritoneal dialysis samples demonstrated linezolid concentrations greater than 4 microg/ml at the end of 4- or 8-hour dwell times, except for one level after a missed dose on linezolid treatment day 3. Duration of dwell times did not appear to correlate with linezolid concentrations. CONCLUSION: In this patient, linezolid 600 mg twice/day penetrated into peritoneal dialysis fluid at or above the concentrations necessary to treat common gram-positive bacteria. Linezolid therapy is likely to have a role in peritoneal dialysis-associated peritonitis based on its antimicrobial activity, pharmacokinetic properties, ease of administration, and tolerability.     

Pharmacokinetics of intraperitoneal teicoplanin in patients with chronic renal failure on continuous ambulatory peritoneal dialysis.

The pharmacokinetic profile of teicoplanin, a new glycopeptide antibiotic active against Gram-positive aerobic and anaerobic bacteria, is described in five patients with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD). A single 3 mg kg-1 dose was given intraperitoneally in the dialysate during a 6 h dwell time. The drug appeared in the plasma within 15 min at 1.00-0.28 mg l-1 (mean +/- s.d. = 0.70 +/- 0.45) in all five subjects, and peak serum concentrations ranged from 5.53 to 2.80 mg l-1 (4.84 +/- 1.43) at 6 h. Approximately 70% (71 +/- 12) of teicoplanin was absorbed from the peritoneal dialysis fluid during a single 6 h dwell time. The rate constant for peritoneal transfer (lambda d) averaged 0.318 h-1 and the half-life (t1/2 lambda d) was 2.18 h. Further values were serum elimination half-life 114-173 h; total body clearance 263-532 ml h-1; steady-state volume of distribution 68-93 l. This drug profile closely agrees with data reported after intravenous injection in patients on CAPD and suggests that teicoplanin has bidirectional exchange characteristics through the peritoneal membrane, although transfer from the systemic circulation to peritoneal fluid is consistently low. Instillation of teicoplanin in CAPD fluid may be a useful route of administration for treatment of peritonitis and exit site infections in CAPD patients.     

癫痫患者苯妥英钠血药浓度与眼球震颤的关系

观察32例(男20,女12,年龄32±6a)癫痫患者眼球震颤出现及消失与苯妥英钠血浓度的关系,发现(1)出现眼球震颤的血药浓度为37±6μg/mL,提示药物过量;(2)眼球震颤出现在眼球偏斜角度的大小与苯妥英钠血浓度有关,浓度越高,角度越小,在≤45°组为48±3μg/mL,在>45°组则为35±5μg/mL;(3)眼球震颤消失时的血药浓度在20μg/mL左右。     

Clearance calculations in hemodialysis: Application to blood,plasma, and dialysate measurements for ethambutol

With the increasing use of artificial kidneys, numerous reports have appeared describing the pharmacokinetics of administered drugs in dialysis patients. Unfortunately, different investigators use different measures of dialysis clearance in reporting their results. Few studies have appeared in which actual measurements have been made in blood and dialysate as well as in plasma to experimentally show the variability of individual measurements and to demonstrate the inaccuracy of certain clearance measurements. We do so here, using the drug ethambutol. The effect of the artificial kidney on the removal of ethambutol was investigated in four uremic patients undergoing chronic hemodialysis. Ethambutol was administered by i.v. infusion over 30 min. Hemodialysis started at the end of drug infusion. Blood, plasma, and dialysate samples were collected periodically over 3 hr and analyzed for ethambutol content. Dialysis clearance was calculated by arterialvenous difference and by simultaneous dialysate measurement. The extraction efficiency of the hollow fiber dialyzers ranged from 36.2% to 43.8% in terms of blood and from 38.0% to 45.4% in terms of plasma. The mean clearance values due to dialysis were 108.08 and 88.1 ml/min measured with plasma and blood as body fluids of reference, respectively. Dialysis clearance calculated by dialysate measurement had a mean of 85.9 ml/min expressed as plasma and 74.7 ml/min expressed as blood. This study demonstrates that dialysis clearance when calculated using A-V difference and plasma flow is generally underestimated, particularly for a drug which extensively partitions into red blood cells. Ethambutol had a partition coefficient (blood/plasma) of greater than 1 in all four patients. The phase exhibited a mean half-life of approximately 2 hr on dialysis in comparison to off dialysis half-lives of 7 hror longer in renal failure. Although ethambutol exhibits a markedly reduced half-life of the drug during hemodialysis, its recovery in the dialysis fluid during a 3-hr dialysis period constitutes only a small fraction of the dose administered.This work was supported in part by NIH Grant GM 26551.     

Gastrointestinal Dialysis of Digoxin Using Cholestyramine

Abstract: The pharmacokinetic parameters of digoxin given intravenously (0.075 mg/kg) alone and following treatment with oral cholestyramine (8 gm in 50 ml water) were studied in rabbits. Pretreatment with cholestyramine produced a significant decrease in the serum concentration of digoxin and significantly enhances its systemic clearance as indicated by a statistically significant decrease in the area under the concentration-time curve (AUC), half time of elimination (t_1/2), and mean residence time (MRT). These findings indicate that the idea of gastrointestinal dialysis, known with activated charcoal, could be extended to ion-exchange resins that could be a potentially useful adjunctive measure in the management of drug overdose especially with commonly used drugs with a low therapeutic index like digoxin.     

Pharmacokinetics of intravenous and intraperitoneal ceftriaxone in chronic ambulatory peritoneal dialysis

Summary The kinetics of ceftriaxone was investigated in 8 patients without infection, who were receiving continuous ambulatory peritoneal dialysis (CAPD). Ceftriaxone 1 g was injected i.v. and 1 g was given intraperitoneally in the CAPD fluid during a 4-h dwell time. Ceftriaxone was assayed by HPLC. After intravenous administration, the kinetic parameters of ceftriaxone were: plasma t_1/2, 12.3 h, total plasma clearance, 14.0 ml/min, volume of distribution at steady state 0.18 l/kg, and peritoneal clearance 0.59 ml/min. Over 72 hours only 5.5% of the dose was eliminated by the peritoneal route. After intraperitoneal administration, ceftriaxone rapidly appeared in serum; the absorption t_1/2 was 1.1 h and the mean peak concentration was 38.8 µg/ml. The absorption of ceftriaxone from the peritoneal space was 39%. A single 1.0 g IP dose led to serum and dialysate concentrations of ceftriaxone above the minimum inhibitory concentration for susceptible pathogens for 24 hours.     

平阳霉素对HeLa细胞DNA的体外断裂作用

用琼脂糖电泳及DNA电镜技术观察平阳霉素对HeLa细胞DNA的体外断裂作用。药物处理的DNA经琼脂糖电泳及溴乙锭染色后,紫外荧光摄影。0.5μg DNA与5μg/ml药物作用2h及200μg/ml作用10min即可见DNA断裂。应用碱性蛋白膜展层法制作DNA电镜标本,5μg/ml DNA与10μg/ml药物作用2h可见自然弯曲的DNA长链(±SD=5.97±1.95μm)被切割成DNA短段(±SD=0.73±0.24μm),对照组DNA长度长于药物处理组(P<0.01)。     

Stability of dobutamine hydrochloride in peritoneal dialysis solutions

The stability of dobutamine hydrochloride in peritoneal dialysis solutions at 4, 26, and 37 degrees C was determined. Dobutamine (as the hydrochloride salt) was added to dialysis solutions containing 1.5% or 4.25% dextrose to concentrations of 2.5, 5.0, and 7.5 mg/mL. Samples were stored at 4, 26, and 37 degrees C to mimic refrigerator, room, and body temperature, respectively. At 0, 4, 8, and 24 hours, the samples were analyzed in triplicate by stability-indicating high-performance liquid chromatography to determine the percentage of drug remaining. More than 90% of the drug was retained under all storage conditions in 1.5% dextrose dialysate containing an initial dobutamine hydrochloride concentration of 5.0 or 7.5 micrograms/mL. The mean concentration in the samples containing an initial dobutamine hydrochloride concentration of 2.5 micrograms/mL and stored at room temperature remained greater than 90% of the initial concentration for the first four hours and then decreased to less than 90%. Dobutamine was stable in 4.25% dextrose dialysate regardless of the initial concentration or the storage condition. Dobutamine hydrochloride 5.0 and 7.5 micrograms/mL in 4.25% dextrose dialysis solution was stable under all the test conditions. Dobutamine hydrochloride 2.5 micrograms/mL was stable in 1.5% dextrose dialysate for only four hours at room temperature.     

Ceforanide pharmacokinetics in haemodialysis: the effect of ultrafiltration

The kinetics of ceforanide in plasma and dialysate was studied in 8 patients with terminal renal impairment after undergoing haemodialysis sessions lasting between 4 and 5 h. All patients received a single i.v. dose of 15 mg kg-1 of the drug at the start of the session. The dialysers used in this study were Spiraflow capillar 1.3 m2, Travenol plates 1.4 m2, and PAN plates. Blood flow ranged between 200 and 300 ml min-1 and dialysate flow between 500-650 ml min-1. Plasma ceforanide levels were measured at the input and output of the dialyser and the antibiotic levels in dialysate were determined coinciding with the withdrawal times of the blood samples. A microbiologic plate diffusion method was used to determine the antibiotic concentrations. The mean values of some pharmacokinetic parameters of ceforanide calculated with a non-linear regression program from the data obtained from arterial blood were the following: alpha (h-1) = 4.14 +/- 1.32; beta (h-1) = 0.26 +/- 0.07; t1/2 beta (h) = 2.82 +/- 0.82; Vdss (1) = 10.24 +/- 2.14. From the relationships between the antibiotic concentrations at the input and output of the dialyser it was possible to calculate an extraction coefficient of 0.11 +/- 0.06. The dialysis clearance of ceforanide was calculated from the determination of the extraction coefficient and from the measuring of antibiotic in dialysate, though different results were obtained with the two methods. Dialysis clearance calculated from the extraction coefficient showed a mean value of 18.68 +/- 12.16 ml min-1, significantly lower (p less than 0.01) than that established by analysis of the antibiotic in dialysate, which was 41.55 +/- 15.83 ml min-1. These differences may be attributed to problems related to the determination of blood flow and to the ultrafiltration capacity of the dialysis membranes. A linear relationship was established between the percentage error in the observed and predicted extraction coefficients and the ultrafiltration rate. The results obtained suggest that the simultaneous measurement of the antibiotic in plasma and dialysate is the most suitable method for predicting the dialysis clearance of the drug. The amount of antibiotic extracted over a 4-hour dialysis session proved to be equal to 57.85 +/- 15.62 per cent of the dose administered.