人尿中曲马多及其代谢物的分析

用GC-MS方法分析了人尿中的曲马多及其代谢产物。分析步骤:尿用酸解、醚洗及二氯甲烷—异丙醇混合溶剂提取,挥干后用MSTFA-MBTFA衍生化,然后于GC-MSD上进样分析,在服药后40 h内的尿中可检出原型及4个代谢物,在40～60 h内只能检出原型。本法对原型药物的回收率为85.2%,检测限可达12.5 pg。     

血、尿中氯氮平的提取检验方法探讨

目的建立血、尿液中氯氨平的提取和检验方法。方法血、尿在碱性条件下用乙醚提取。然后用GC／NPD、GC／MS检验。结果从误服者的血、尿液中均检出氯氨平成分。结论本方法能有效、快速、准确提取和检验血、尿及其他检材中的氯氮平：已用于医疗急救、办案工作中。获得了满意结果。     

高效液相色谱法测定尿中庆大霉素含量

本文研究了尿中庆大霉素的高效液相色谱测定法。将尿样用缓冲液稀释,以二氯甲烷除去尿中干扰物,水相中的庆大霉素经邻苯二醛衍生化,再用醋酸乙酯提取。提取物经色谱柱分离后荧光检测。线性范围为50～500μg/ml,平均回收率为96.2%,日内变异系数低于5%,最低检出浓度为5μg/ml。     

痛炎速灵片的生物利用度及药物动力学

用紫外分光光度法测定尿中痛炎速灵的浓度。在pH5.8磷酸盐缓冲液中,以氯仿为提取剂,测定波长317±1nm,测得平均回收率为95.5±2.5%,CV=2.6%.检测浓度范围2～20μg/ml,重现性好,专一性强。人口服片剂和溶液消除半衰期分别为2.52±0.35h和2.78士0.70h,尿中回收原型药物占给药量的百分率分别为82.3±11.0%和87.4±7.1%.片剂的相对生物利用度为94.0±7.2%.     

抗溃疡药奥美拉唑(Omeprazole)

用妊娠羊研究显示,奥美拉唑易通过胎盘、胎羊的药物浓度为母羊的50%。狗、大鼠、小鼠口服单剂量〔~(14)C〕-奥美拉唑,72小时尿中放射活性的排泄量分别为38、43和55%,其余大多从粪中排出,尿中未见有药物原形。代谢产物有10种以上,胆道为代谢物的主要排泄途径。 5例健康受试者口服60mg〔~(14)C〕-奥美拉唑,96小时内从尿排泄总量的83%,开始2小时内排泄达47%,尿中可见6种代谢物,未检出药物原形。二种主要代谢物的代谢途径为吡啶环甲基的羟化与继而氧化成相应的羧酸。饭后给药其吸收延迟,但不影响吸收     

120株肠球菌耐药分析及药物选择

目的观察肠球菌属的临床分布特点及耐药状况。方法收集医院2011年1月～6月培养检出的120株肠球菌属,分析其在各种临床标本中的分布特征和耐药状况。结果检出粪肠球菌63株(52.5%)、屎肠球菌48株(40.8%)、其他肠球菌8株(6.7%)。其中尿液中检出58株肠球菌(48.3%)。屎肠球菌的耐药率普遍较粪肠球菌高。未检出耐万古霉素的尿肠球菌和粪肠球菌,检出耐利奈唑胺粪肠球菌2株。结论肠球菌属感染以粪肠球菌和屎肠球菌为主,肠球菌属中各种菌对抗菌药物的耐药性有差异,应在抗菌药物敏感试验指导下并结合感染部位合理地选用抗菌药物。     

阿片类药物依赖性患者尿标本中吗啡的薄层色谱检定法研究

本文报告阿片类药物依赖性患者尿标本中吗啡的薄层色谱检定法。尿标本在酸性条件下沸水浴中水解,经有机溶剂提取纯化后,进行薄层分析。薄层板为硅胶GF-254。比较了两种展开剂系统和两种提取溶剂。检测方法用紫外分析灯和Dragendorff试剂显色。应用本法检测尿中吗啡的检测限为2μg。特异性好,一些常见合并用药不干扰吗啡测定。用本法检测72例阿片类药物依赖性患者约200份尿标本的结果表明,停用毒品后24～48小时可检出其中的吗啡。本法所得结果准确,操作简便,所需仪器条件低,适合大面积应用于阿片类药物滥用的流行学调查和该类患者的诊断与治疗过程中的监测。     

诺乙龙体内代谢物的GC-MS分析鉴定

GC-MS联用分析诺乙龙阳性尿,检出了诺乙龙经人体吸收代谢以后产生的九个代谢产物。除Met-2和Met-7在服药后84h的尿样中仍能被检出以外,诺乙龙原型及其它代谢物的体内存留时间较短,可检测时间不超过35h。通过解析质谱,鉴定了七个代谢物的分子结构,发现A环双键还原和D环羟基化是诺乙龙的两种体内代谢途径.用大孔树脂吸附提取、酶解、衍生化等处理尿样,方法回收率达80%,诺乙龙的检测下限为10ng/ml(10 ppb).     

血、尿中安眠酮及其代谢物的测定

通过一例安眠酮中毒病人血、尿中安眠酮及其代谢物的测定,描述了用紫外光谱(uv)、气相色谱(GC)和气相色谱质谱(GC/MS)法测定安眠酮及其代谢物的系统分析方法。样品的提取净化采用液一液萃取和固相萃取两种方法,都得到了很好的结果。紫外光谱用于测定血、尿中安眠酮和其代谢物的总量;气相色谱用于测定血、尿中安眠酮原药的含量;气相色谱质谱则用于鉴定血、尿中的安眠酮及其代谢物。除安眠酮外,血、尿中共检出10种安眠酮代谢物,其中包括两种乙酰化代谢物。此法还为临床救治提供指导。     

尿培养常见病原菌分布及耐药性分析

目的：分析尿培养分离常见病原菌的分布特点及其耐药性。方法对2010年6月至2014年6月送检的中段尿细菌培养阳性标本进行分析,统计分离常见病原菌的种类特点、构成比和耐药性。结果尿培养阳性标本中共分离出1194株病原菌,其中革兰阴性菌786株（65.83%）;革兰阳性菌304株（25.46%）,其以肠球菌属为主,粪肠球菌和屎肠球菌最多见;真菌104株（8.71%）。在所有病原菌中,大肠埃希菌检出最多,为571株（47.82%）。另外,检出产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯菌分别为232株（40.63%）和27株（32.53%）。肠杆菌科细菌对碳青霉烯类抗菌药物敏感率在90%以上,铜绿假单胞菌和鲍曼不动杆菌对哌拉西林/他唑巴坦耐药率为10.34%和8.33%。结论尿培养病原菌以革兰阴性菌为主,大肠埃希菌最常见;常见病原菌耐药形势严峻,临床应重视细菌培养,根据尿培养结果,合理使用抗菌药物。     

Direct assay of conjugates of penbutolol and its metabolites in urine

The metabolites of 1-tert.-butylamino-3-(2-cyclopentylphenoxy)propan-2-ol (penbutolol, Betapressin), penbutolol 2-glucuronide, 4'-OH-penbutolol 2-glucuronide, 4'-OH-penbutolol 4-sulfate and 1"-dehydropenbutolol 2-glucuronide were determined in urine by high-performance liquid chromatography (HPLC). The compounds were determined after direct injection, that is to say without prior cleavage of the conjugates to the corresponding aglycones. In the case of the glucuronides, the urine was injected into the HPLC system without further sample preparation. The sulfate was determined after ion-pair extraction. Fluorimetric detection was employed. Depending on the compound, the detection limits lay between 0.07 and 0.3 micrograms/ml. This method was used to determine the cumulative urinary excretion of a subject.     

Isolation, identification and in vitro synthesis of conjugates of penbutolol and its metabolites

The metabolites of 1-tert.-butylamino-3-(2-cyclopentylphenoxy)propan-2-ol (penbutolol Betapressin) penbutolol 2-glucuronide, 4'-OH-penbutolol 2-glucuronide, 4'-OH-penbutolol 4'-sulfate and 1'-dehydropenbutolol 2-glucuronide were isolated from the urine of patients, purified by high-performance liquid chromatography and characterised by 1H-NMR and mass spectroscopy. Penbutolol 2-glucuronide and 4'-OH-penbutolol 4'-glucuronide were synthesised in vitro from penbutolol and 4'-OH-penbutolol, respectively, using glucuronyltransferase.     

Pharmacokinetics of penbutolol and its metabolites in renal insufficiency

Summary The pharmacokinetics of penbutolol, its 4-hydroxylated metabolite and of their conjugates was studied in hypertensive patients with various degrees of renal impairment.A single oral dose of penbutolol 40 mg, was rapidly absorbed after a lag-time of 0.34 h. Its plasma concentration reached a maximum after 0.84 h and then declined bi-exponentially, with an apparent elimination half-life of 21.8 h. The hydroxylation of penbutolol was negligible and conjugation was of major importance for its elimination. Consequently, the kinetics of unchanged penbutolol were not altered by renal impairment. The 48 h-urinary excretion of penbutolol and its metabolites reached 13–14% of the administered dose, which is consistent with extensive metabolism of the drug.After treatment for 30 days with penbutolol 40 mg/d there was no accumulation of the parent drug but the concentration of its conjugates was increased.It is concluded that the dose of penbutolol need not be changed in patients with mild renal insufficiency, 4-hydroxypenbutolol is unlikely to participate in the anti-hypertensive effect of the drug, due to its low concentrations, and biotransformation of penbutolol may be enhanced during chronic treatment.     

Penbutolol: Pharmacokinetics,effect on exercise tachycardia,and in vitro inhibition of radioligand binding

Summary The pharmacokinetics of penbutolol 40 mg, its reduction in exercise-induced tachycardia, and the in vitro inhibition of radioligand binding to beta-adrenoceptors by plasma have been investigated in 7 healthy volunteers.The peak penbutolol concentration of 285 ng/ml was observed 1.2 h after administration, and the maximum of 4-OH-penbutolol of 4.76 ng/ml was found after 1.64 h. Penbutolol was detected for up to 48 h, and 4-OH-penbutolol dropped below the limit of detection after about 10 h. The terminal plasma concentration of penbutolol declined with an average half-life of 19 h.The maximum reduction in exercise-induced tachycardia was 33 beats/min 2.6 h after taking penbutolol. There was still a significant reduction of about 7 beats/min after 48 h. This effect could be adequately explained by the concentration-time course of penbutolol in combination with Clark's model of the concentration-effect relationship.Antagonist activity in plasma caused 91% inhibition of radioligand binding in vitro to beta₂-adrenoceptors on rat reticulocyte membranes 1.6 h after intake of penbutolol. By 48 h after intake, radioligand binding was still significantly inhibited (23%). The in vitro inhibition of radioligand binding by plasma showed a linear correlation with the reduction in exercise-induced tachycardia for all phases of the workload. The time course of the reduction in heart rate was completely explained by the in vitro inhibition of radioligand binding. However, it was not possible to explain the in vitro inhibition of radioligand binding by the concentration-time course of penbutolol using a simple competition model, although both variables were based on the same sampling site. When the in vitro inhibition of radioligand binding was plotted against the penbutolol concentration at the same sampling times (with both variables transformed to multiples of the apparent inhibition constant) the discrepancy became even more apparent as time-related counterclockwise hysteresis.None of the known metabolites of penbutolol can explain the discrepancy between the penbutolol concentration and the inhibition of radioligand binding in vitro. It appears that an other active metabolite is formed, which contributes to the effect in vitro and in vivo and so can explain the observed discrepancy.Dedicated to Professor Dr. med. U. Trendelenburg, Würzburg, on the occasion of his 65th birthdaySome of the results were presented at the Xth International Congress of Pharmacology (IUPHAR), Sydney, 1987     

Comparative beta-adrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man.

1 The beta-adrenoceptor blocking effects of penbutolol were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 7 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and plasma levels of penbutolol and propranolol were determined. 3 Penbutolol proved to be a non-cardioselective beta-adrenoceptor blocking drug, antagonizing exercise-induced tachycardia, reducing exercise-induced increase in PEFR and decreasing PRA. The beta-adrenolytic potency of penbutolol was shown to be four-fold that of propranolol but the duration of its effect was similar. 4 The peak plasma level of penbutolol was reached 1 h after administration and its half-life was 4.5 h. 5 Comparison of plasma levels and biological activity of penbutolol revealed that after oral administration this drug is transformed into an active metabolite in man.     

Penbutolol pharmacokinetics: the influence of concomitant administration of cimetidine

Summary A possible interaction of penbutolol and cimetidine was investigated in healthy volunteers treated orally for 7 days.The plasma levels of unmetabolised penbutolol showed a slight but non-significant increase. The biphasic elimination kinetics of penbutolol (half-lives 0.8 and 17 h) was not affected by coadministration of cimetidine. Plasma levels of penbutolol were not significantly altered by chronic treatment with cimetidine, whereas the levels of 4-hydroxypenbutolol and 4-hydroxypenbutolol glucuronide were significantly reduced.     

Long term treatment of moderate hypertension with penbutolol (Hoe 893d). I. Effects on blood pressure,pulse rate,catecholamines in blood and urine,plasma renin activity and urinary aldosterone under basal conditions and following exercise

Summary The effects of penbutolol (Hoe 893 d), a new non-selective beta-receptor blocking agent, were studied in 5 patients with moderate hypertension. Initially, it was shown that 2–4 mg given orally once or twice daily tended to lower blood pressure and pulse rate, both at rest and following submaximal work. In prolonged trials (3–8 months) 40–60 mg/day were required to produce an acceptable antihypertensive effect. Penbutolol had no effect on the normal increase in plasma noradrenaline and adrenaline on standing, nor did it alter basal urinary catecholamine excretion. Submaximal work caused no significant change in plasma catecholamines before treatment, but there was a marked rise both in plasma noradrenaline and adrenaline during treatment with penbutolol. In short term studies there was a fall in plasma renin by 4 hours after oral administration of penbutolol 2–4 mg, which persisted for 24 hours. Prolonged treatment with penbutolol 20–30 mg twice daily inhibited renin production under basal conditions and following submaximal work, as well as lowered basal urinary aldosterone excretion. In one patient slight asthmatic symptoms appeared after treatment for 3 months with penbutolol. In other respects penbutolol was well tolerated.     

Biotransformation of linogliride,a hypoglycemic agent in laboratory animals and humans

Following oral administration of linogliride, a hypoglycemic agent, to rat (50 mg kg⁻¹), dog (30 mg kg⁻¹), and man (100 mg per subject), plasma, urine, and fecal extract sample pools were obtained. Nine metabolites plus unchanged linogliride were isolated and identified. The number of metabolites identified were: rat (5), dog (9), and man (1). In each species, more than 78% of the administered dose was recovered in the urine pools. Identified metabolites were estimated to account for >82% of the total amounts of drug-related sample in urine pools and >50% in plasma and fecal extract pools.Formation of linogliride metabolites in the three species can be described by four proposed pathways: pyrrolidine hydroxylation, aromatic hydroxylation, morpholine hydroxylation, and imino-bond cleavage. Comparison of the proposed metabolic pathways among species reveals a similarity between rat and dog. In these two species, pyrrolidine hydroxylation was quantitatively the most important pathway, with 5-hydroxylinogliride and dominant hypoglycemic active metabolite in all sample pools. Further oxidation of 5-hydroxylinogliride resulted in the formation of five minor metabolites. The other three pathways appeared to be quantitatively unimportant.Metabolism of linogliride in man occurred to a very limited extent. More than 90% of the total linogliride-related material in plasma was the unchanged drug. Greater than 76% of the administered dose was excreted unchanged in the urine. Only 5-hydroxylinogliride was identified in minor amounts in human samples.     

Long term treatment of moderate hypertension with penbutolol (Hoe 893d) III. Effects on glucose tolerance and insulin production

Summary Studies in seven patients with moderate hypertension were done to explore the effect of the non-selective beta-receptor blocking agent penbutolol on blood glucose and plasma insulin levels under fasting conditions, and following a glucose load. Oral penbutolol 20–30 mg, twice daily for 3–8 months, produced no change in fasting levels of blood glucose and plasma insulin, or in the blood glucose response following an oral or iv glucose load. The initial insulin response to intravenous glucose was similar before and during penbutolol treatment. The total integrated insulin response following iv glucose increased slightly during treatment when measured from insulin zero level, but was unaltered when calculated from the initial basal insulin level. Following oral glucose the total integrated insulin response was not affected by treatment with penbutolol.     

A rapid, sensitive assay for cocaine and its metabolites in biological fluids using solid-phase extraction and high-performance liquid chromatography

An improved method for the simultaneous determination of cocaine and its metabolites, benzoylecgonine (BE), norcocaine, and ecgoninemethylester (EME), in rat plasma and urine is described. Following derivatization of EME to p-fluorococaine, chromatography was performed on two high-performance liquid chromatography (HPLC) columns in series (5-microm spheric C8 and 5-microm cyanopropyl) using a mobile phase containing acetonitrile/HPLC water/trifluoroacetic acid (28:72:0.1) with bupivacaine as an internal standard. Quantitation limits were 25 ng/mL for cocaine, BE, and norcocaine and 50 ng/mL for EME using 300-500 microL rat plasma and 500 microL of rat urine. The assay was linear from the limit of quantitation to 2000 ng/mL for cocaine and its metabolites in both plasma and urine samples. Because this method uses a small amount of sample (300 microL plasma or 500 microL of urine), it is applicable to study of the pharmacokinetics and disposition of cocaine and its major metabolites.