舒氨西林治疗血液病并发感染24例

应用国产舒氨西林与氨苄西林随机对照治疗血液病合并感染患者４８例，结果舒氨西林临床有效率８３．４％，明显优于氨苄西林５０．０％，不良反应轻微。     

新型口服青霉烯类抗生素法罗培南的抗菌活性和对呼吸系感染的临床疗效

因法罗培南的母核具有理想的５环结构,２－位为双键结合,４－位为Ｓ,所以口服吸收好,对青霉素结合蛋白富有生物活性。小山优对口服青霉烯类抗生素法罗培南的抗菌力及其对呼吸系感染的有效性与其它内酰胺类口服抗生素进行了比较研究。法罗培南对肠球菌的抗菌活性与氨苄西林相当。对革兰氏阴性菌的活性与头孢类抗生素相近,对流感嗜血菌的活性比氨苄西林、舒氨西林强,较头孢特仑、头孢克肟等第Ⅲ代头孢菌素稍弱,对莫拉氏菌、粘膜炎布兰汉氏球菌的活性,介于第Ⅱ、Ⅲ代头孢菌素之间;对肺炎克雷伯氏菌的活性则在第Ⅰ、Ⅲ代头孢菌素之间。…     

洛美沙星在呼吸系感染中的应用

洛美沙星在呼吸系感染中的应用吴抗美（杭州市第二人民医院杭州３１００１５）洛美沙星（Ｌｏｍｅｆｌｏｘａｃｉｎ）是第三代喹诺酮类药物的新品种，经临床观察，口服洛美沙星与静脉滴注氨芋西林及阿米卡星在治疗慢性支气管炎急性发作患者中，洛美沙星的疗效优于氨苄西林...     

盐酸仑氨西林片与阿莫西林胶囊治疗急性细菌性感染随机双盲双模拟对照临床试验

目的 评价盐酸仑氨西林片和阿莫西林胶囊治疗呼吸道及皮肤软组织感染的安全性和有效性。方法 用双盲双模拟随机对照方法,治疗急性上呼吸道感染、皮肤软组织感染。剂量均为0.5g,tid,疗程7～14天。结果 共入选合格病例141例,其中仑氨西林组73例,痊愈率和有效率分别为71.2%和91.8%;对照组阿莫西林胶囊组68例,痊愈率和有效率分别为70.6%和94.1%;药物不良反应发生率仑氨西林组为6.9%,阿莫西林胶囊组为7.4%,2组临床疗效和药物不良反应均无统计学差异。结论 盐酸仑氨西林和阿莫西林是治疗常见急性细菌性呼吸道感染及皮肤软组织感染的较为安全、有效的抗菌药物。     

复方氨氯西林胶囊在健康志愿者中的药动学

目的研究在中国健康志愿者中口服复方氨氯西林胶囊的药动学。方法12名健康志愿者,按拉丁方设计随机分组,分别口服复方氨氯西林胶囊0.5,1.0和2.0 g,采用液相色谱串联质谱法检测给药后的血药浓度,DAS1.0软件计算药动学参数。结果健康受试者单剂量口服复方氨氯西林胶囊0.5,1.0,2.0 g,氨苄西林和氯唑西林药-时曲线符合一房室模型,权重采用I/C/C。氨苄西林主要药动学参数分别为t_(1/2)(0.99±s 0.15)、(1.03±0.15)、(1.2±0.3)h;AUC_(0～t)(18±4)、(31±10)、(44±11)mg·h·L~(-1)。氯唑西林主要药动学参数分别为t_(1/2)(1.1±0.3)、(1.12±0.27)、(1.08±0.14)h;AUC_(0～t)(2.3±0.6)、(5.1±1.1)、(10.2±2.0)mg·h·L~(-1)。氨苄西林和氯唑西林各剂量组药动学参数除c_(max)、AUC_(0～t)、AUC_(0～∞)外,t_(max)、t_(1/2)、Ke、MRT差异均无统计学意义,c_(max)、AUC_(0～t)、AUC_(0～∞)均与给药剂量呈线性相关(P<0.01)。结论12名健康受试者分别口服复方氨氯西林胶囊后,在0.5 g～2 g剂量范围内呈线性人体药动学特征。     

健康人口服复方氨氯西林胶囊尿药排泄及药动学分析

目的：建立高效液相色谱-串联质谱联用法（LC—MS／MS）同时测定人尿中氨苄西林和氯唑西林浓度,研究健康人口服复方氨氯西林胶囊后的尿药排泄。方法：12名健康男性志愿者按3×3拉丁方顺序进行单剂口服给药后按设计时间点收集尿样。尿样加入曲马多为内标,甲醇沉淀蛋白后进样,分析氨苄西林和氯唑西林的浓度,色谱条件为：色谱柱：Shim—packVP—ODS柱（150mm×4．6mm,5μm）;流动相：甲醇-10mmol·L。乙酸铵（68：32）;流速：0．8ml·min-1;采用等度洗脱进行分离,质谱检测采用多重反应监测（MRM）扫描。结果：氨苄西林和氯唑西林线性范围分别为：0．10～15．00μ-ml-1和0．05—10．00μg·ml-1,线性关系均良好。准确度与精密度结果显示高、中、低三种浓度的氨苄西林和氯唑西林日间、日内变异均小于15％。24h、内氨苄西林低、中、高剂量组的原形药物平均累积排泄率分别为（38．04±16．6）％,（31．7±15．9）％,（28．24±8．0）％;氯唑西林低、中、高剂量组平均累积排泄率分别为（11．3±3．9）％,（10．7±3．6）％,（11．2±4．3）％。结论：本法可用于同时测定人尿中氨苄西林和氯唑西林浓度,复方氨氯西林胶囊中氨苄西林在人体内排泄与单药时一致,氯唑西林在人体内主要以非原形药排泄。     

口服珍欣片治疗小面积烧伤创面感染的临床疗效观察

以往治疗小面积烧伤创面感染使用抗生素途径主要为静脉注射，其次为肌肉注射，口服途径给药较为少见。珍欣（盐酸仑氨西林）片是新型半合成青霉素类广谱抗生素，我们于2004年7月至2005年7月期间采用国产珍欣片治疗小面积烧伤创面感染，获得可较好的治疗果，现报告如下：     

2009 年至 2011 年我院药品服务部口服抗生素用药分 析简

目的探讨医院口服抗生素应用的规律性。方法对医院2009年至2011年药品服务部口服抗生素的销售金额、用药频度（DDDs）及限定日费用（DDC）等进行统计。结果3年来,头孢地尼胶囊、盐酸仑氨西林片、盐酸莫西沙星片、头孢地尼分散片在用药频度上排前列。结论在抗生素的临床应用上,比较偏向于使用较新品种的抗生素,应严格适应证使用。     

氨砜西林注射液中氨苄西林和舒巴坦的HPLC测定

用反相高效液相色谱外标法同时测定氨砜西林注射液中氨苄西林和舒巴坦的含量，以０．０１ｍｏｌ／Ｌ磷酸二氢钾（内含７％乙腈）为流动相，于２３０ｎｍ波长处检测，方法简单，重现性好。     

氨砚西林注射液中氧苄西林和舒巴坦的HPLC测定

用反相高效液相色谱外标法同时测定氨砜西林注射液中氨苄西林的舒巴坦的含量，以０．０１ｍｏｌ／Ｌ磷酸二氢钾（内含７％乙腈）为流动相，于２３０ｎｍ波长处检测，方法简单，重现性好。     

Ampicillin concentrations in human oral tissues following a single oral administration of lenampicillin.

1. Ampicillin concentrations in serum (n = 20), gingiva (n = 12), jawbone (n = 13), dental follicle (n = 12), radicular granuloma (n = 2) and radicular cyst (n = 2) were measured in specimens obtained during 0.5-2.5 hr after a single oral administration of lenampicillin (equivalent to 500 mg of ampicillin). 2. Measurable ampicillin concentrations were found in all serum and tissues. 3. Ampicillin concentrations in serum and tissues except for some gingiva and jawbone exceeded MIC for 90% of clinically isolated strains of alpha-hemolytic Streptococci. 4. Ampicillin concentrations in gingiva and jawbone were below the MIC for 90% in 2 out of 12 and 4 out of 13 specimens, respectively.     

Metabolism of lenampicillin hydrochloride. I. Metabolism of ampicillin structure

Metabolism of lenampicillin hydrochloride (LAPC), especially ampicillin (ABPC) structure of LAPC, was investigated after oral administration in human, dogs and rats. The unchanged compound was not detected in blood and urine, furthermore in animal portal vein after oral administration of LAPC in human and 2 animals. Therefore, LAPC seemed to be rapidly hydrolyzed during the process of absorption. The intestinal absorption of LAPC was satisfactory in view of the urinary excretion of metabolites, accounting for 93% of dose in human, 74% in dogs and 55% in rats, respectively. It could be judged by the bioautograms and the correlation between bioassay and HPLC determination of ABPC that the active metabolite in blood or urine was only ABPC. The major urinary metabolites were ABPC, alpha-aminobenzylpenicilloic acid (ABPA) and 5S-penicilloic acid isomer (5S-ABPA) in human and 2 animals, but the differences were observed on the excretion ratio between human, dogs and rats. LAPC was stable in the intestinal contents, but liable to hydrolyze in the intestinal wall, blood and liver of rats. From the facts described above, it was concluded that LAPC was the efficient prodrug of ABPC in terms of the enhancement of absorption and decrease of side effects.     

Clinical evaluation of lenampicillin in oral and maxillofacial infections

Clinical efficacies of newly developed synthetic oral ampicillin prodrug lenampicillin (LAPC, KBT-1585) applied to 109 cases of oral infection were studied. There were 7 dropout cases. The results as determined on a point system are as follow: Remarkably effective, 26 cases; effective, 63 cases; and not effective, 13 cases, for an efficacy rate of 87.3%. When rated by the subjective judgement of the doctors in charge, these figures are as follow: remarkably effective, 21 cases, effective, 67 cases; slightly effective, 10 cases; and not effective, 4 cases. The rate of efficacy in this way being 86.3%. In either way, the results obtained were favorable. Among 102 cases in this study, pus was aspirated with sterile needle from obstructed abscesses in 65 cases, with the result that 161 strains of bacteria were isolated and identified. Most of infections were found mixed type by aerobic Gram-positive cocci and anaerobes. Especially, cases caused by alpha-Streptococcus were observed in 48 out of 55 mixed infective cases. LAPC's MIC distribution against the detected bacteria showed strong antibacterial effect as follows: against Gram-positive cocci, less than 0.39 micrograms/ml; against Gram-negative bacteria (excluding some insusceptible strains), less than 3.13 micrograms/ml. Thus, LAPC demonstrated a superiority when compared to CEX by 4 approximately 128-fold, and when compared to AMPC by about 2-fold. Adverse reactions among the 109 cases consisted of 6 cases of gastro-intestinal disorders including 3 cases of diarrhea. Recognized cases of abnormal laboratory findings were 3 cases out of 76 (3.9%), but none were serious.     

Kinetic assessment of luminal degradation of orally effective prodrugs for rational drug development

Although prodrugging (prodrug derivatization) is a powerful technique for improving the pharmacokinetic characteristics of drugs, the intestinal pharmacokinetics of prodrugs has yet to be elucidated fully. A previous article reported the kinetic requirement of prodrugs to overcome membrane barriers. In the present article, the luminal degradation of prodrugs was kinetically assessed to understand crucial factors in the intestinal absorption of prodrugs and to show a rational development procedure. A kinetic model equation involving luminal degradation clearance (CL_deg) was derived, and CL_deg was estimated according to the equation with in vitro and in vivo reported data of two kinds of ampicillin prodrugs (lenampicillin and pivampicillin) and one acyclovir prodrug (valacyclovir). For lenampicillin ((2,2-dimethyl-1-oxopropoxy)methyl ester derivative), CL_deg was approximately 1.7 times as large as absorption clearance (CL_abs), whereas for pivampicillin ((5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester derivative), CL_deg was approximately one tenth of CL_abs. For valacyclovir (acyclovir prodrug), CL_deg was negligible. These results indicate that not only membrane permeability but also luminal stability should be assessed for the rational development of orally effective prodrugs, and that luminal stabilization can improve the intestinal absorption of prodrugs. A procedure was proposed to develop orally effective prodrugs considered for luminal degradation as well as membrane permeability. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1078–1086, 2010     

盐酸仑氨西林片溶出度测定方法的研究

目的：建立盐酸仑氨西林片的溶出度测定方法。方法：依照《中国药典》，以水500ml为溶出介质，转速50r／min，紫外分光光度法检测，检测波长为256nm。结果：在0．1～0．9mg／ml范围内(r=0．9998)，浓度与吸收度呈良好的线性关系，平均回收率为100．5％，RSD=1．1％。结论：该法操作简便、快速、准确。     

Pharmacokinetics of ampicillin and its prodrugs bacampicillin and pivampicillin in man

Five healthy fasting male subjects were each given single doses of intravenous ampicillin (471 mg), oral ampicillin tablets (495 mg), oral bacampicillin hydrochloride tablets (562 mg ampicillin equivalent), and oral pivampicillin hydrochloride capsules (491) mg ampicillin equivalent) in a crossover experiment. The resulting concentrations of ampicillin were determined in plasma and urine. The pharmacokinetic analysis was made according to a two-compartment open model. The total distribution volume of unbound ampicillin during the disposition phase was 0.247 +/- 0.045 (SD) liter/kg, which is only slightly more than the extracellular fluid, suggesting that tissue binding and intracellular distribution of ampicillin are limited. The bioavailability of the esters bacampicillin (86 +/- 11%) and pivampicillin (92 +/- 18%) was significantly greater than that of ampicillin (62 +/- 17%); however, the difference between the esters was not statistically significant. The adsorption for all drugs given orally proceeded at a constant rate, suggesting zero-order release rates from the products. The adsorption rate was highest for bacampicillin (0.89 +/- 0.39 of dose absorbed per minute), followed by pivampicillin (0.64 +/- 0.19) and ampicillin (0.58 +/- 0.16). Bacampicillin also had the shortest lag time for the start of absorption (7.0 +/- 0.9 min) under the present conditions. Thus, in comparison with ampicillin, the esters have a higher bioavailability, which, in fact, is close to the theoretically highest possible value by clearance concepts. The higher bioavailability in connection with higher absorption rates may be clinically important in ampicillin treatment by the oral route.     

Stability of ampicillin trihydrate suspension in amber plastic oral syringes

The stability of ampicillin trihydrate oral suspension stored in amber plastic oral syringes was studied. Commercially available ampicillin trihydrate powder for oral suspension was reconstituted according to manufacturer's instructions and drawn into 5-mL amber polypropylene plastic oral syringes. The syringes were divided into groups and stored at -20, 4, 25, 60, or 80 degrees C. Powder from two additional lots was similarly reconstituted and packaged and stored at 80 degrees C only to assess interlot variability. Immediately after reconstitution and at specified times during storage, three syringes at each storage temperature were removed and their contents analyzed for ampicillin trihydrate concentration by a spectrophotometric assay. Samples stored at frozen (-20 degrees C) or refrigerated (4 degrees C) temperature retained at least 90% of the initial ampicillin concentration throughout the 47-day study period. Samples stored at room temperature retained at least 90% of the initial ampicillin concentration for 30 days and exhibited an apparent zero-order degradation rate. Samples stored at heated temperatures (60 and 80 degrees C) exhibited an apparent first-order degradation process, with the concentration of ampicillin decreasing to less than 90% of initial concentration within two hours. Reconstituted ampicillin trihydrate powder for oral suspension is stable for at least 30 days when stored at room, refrigerated, or frozen temperature in the amber plastic oral syringes studied. The expiration dates recommended by the manufacturer for ampicillin trihydrate suspension stored in its original container can also be used for reconstituted suspension stored in these amber plastic syringes.     

Pharmacokinetics of ampicillin and its prodrugs bacampicillin and pivampicillin in man

Five healthy fasting male subjects were each given single doses of intravenous ampicillin (471 mg), oral ampicillin tablets (495 mg), oral bacampicillin hydrochloride tablets (562 mg ampicillin equivalent), and oral pivampicillin hydrochloride capsules (491 mg ampicillin equivalent) in a crossover experiment. The resulting concentrations of ampicillin were determined in plasma and urine. The pharmacokinetic analysis was made according to a two-compartment open model. The total distribution volume of unbound ampicillin during the disposition phase was 0.247 ± 0.045 (sd) liter/kg, which is only slightly more than the extracellular fluid, suggesting that tissue binding and intracellular distribution of ampicillin are limited. The bioavailability of the esters bacampicillin (86 ± 11%) and pivampicillin (92± 18%) was significantly greater than that of ampicillin (62 ± 17%); however, the difference between the esters was not statistically significant. The absorption for all drugs given orally proceeded at a constant rate, suggesting zero-order release rates from the products. The absorption rate was highest for bacampicillin (0.89 ± 0.39% of dose absorbed per minute), followed by pivampicillin (0.64 ± 0.19) and ampicillin (0.58 ± 0.16). Bacampicillin also had the shortest lag time for the start of absorption (7.0 ± 0.9 min) under the present conditions. Thus, in comparison with ampicillin, the esters have a higher bioavailability, which, in fact, is close to the theoretically highest possible value by clearance concepts. The higher bioavailability in connection with higher absorption rates may be clinically important in ampicillin treatment by the oral route.This work was supported by the Swedish Medical Research Council, Project No. 522 (L. O. B.).