头孢他美酯与头孢克肟随机对照治疗细菌性感染疗效分析

对４０例下呼吸道及泌尿道感染患者分别使用头孢他美酯和头孢克肟进行了胡机对照临床观察。     

Effects of sugar ester and hydroxypropyl methylcellulose on the physicochemical stability of amorphous cefditoren pivoxil in aqueous suspension

The improvement in physicochemical stability of amorphous cefditoren pivoxil (CDTR-PI) in aqueous suspensions by addition of sugar ester (SE) and hydroxypropyl methylcellulose (HPMC) was explained by prolonging the induction period prior to crystallization and the reduction in crystal peak intensity. Furthermore, the stabilizing effect of these additives in a multiple additive system was greater than in a single additive system. To determine the mechanism, by which these additives stabilized the amorphous CDTR-PI, we evaluated the surface states of CDTR-PI in suspension by measuring Raman spectra and zeta potential. The change in Raman spectra demonstrated that SE and HPMC interacted with CDTR-PI at the same interaction sites on CDTR-PI. The zeta potential reflected the adsorption phenomena of the additives and indicated that both SE and HPMC adsorbed onto particles of CDTR-PI with no apparent competitive interaction and the response was complementary. It was considered, based on this study, that HPMC and SE would stabilize amorphous CDTR-PI by different mechanisms; HPMC would mainly inhibit crystal growth by small amount of adsorption and SE would inhibit both crystal growth and nucleation by large amount of adsorption. This was considered to result in the hybrid effect in the multiple additive system.     

头孢妥仑匹酯治疗下呼吸道感染性疾病疗效观察

目的：评价头孢妥仑匹酯片治疗下呼吸道感染性疾病的临床疗效及安全性。方法：120例下呼吸道感染的患者随机分为治疗组60例、对照纽60例,分别给予头孢妥仑匹酯和头孢克肟口服,1次200mg,bid治疗,疗程7～14d。结果：头孢妥仑匹酯和头孢克肟组的总有效率分别为95％和83％,细菌清除率为94．2％和66．7％,不良反应发生率分别为3．3％和6．0％,2组差别有统计学意义（P〈0．05）。结论：头孢妥仑匹酯片治疗下呼吸道感染疗效好。安全性高。     

Pharmacokinetics of oral cefetamet pivoxil (Ro 15-8075) and intravenous cefetamet (Ro 15-8074) in humans: a review

Summary

Cefetamet pivoxil belongs to the class of orally absorbed pro-drug esters which are hydrolyzed to the active compound (cefetamet) on their first pass through the gut wall and/or the liver. The intravenously administered cefetamet is eliminated predominantly unchanged in the urine by glomerular filtration. Systemic and renal clearance values for cefetamet were 140 and 130 ml/min, respectively. The plasma protein binding is 22%, whereby the only binding protein is albumin. The steady state volume of distribution (0.29?l/kg) corresponds roughly to the extracellular water space which is consistent with other low protein-bound cephalosporins. In general, after intravenous doses, cefetamet follows the kinetic behaviour of a cephalosporin with low protein binding, limited non-renal clearance, and renal clearance that is predominantly due to glomerular filtration, e.g. ceftizoxime, ceftazidime. After oral administration, cefetamet pivoxil shows a significant food effect (F = 41% vs 51%). Hence, cefetamet pivoxil is recommended to be taken after food. The food effect, however, is not of such a magnitude that it will be of clinical consequence when this recommendation is not followed. The food effect is not related to a change in gastric pH because antacids and ranitidine do not affect the absorption of cefetamet pivoxil, although in approximately 20% of the subjects absorption of the drug is delayed. The elimination of cefetamet is directly proportional to renal function. In patients with varying degrees of renal insufficiencies, dosage should be decreased accordingly. Age has no effect on the bioavailability of cefetamet pivoxil. However, the clearance of cefetamet is higher in children and lower in the elderly.     

Good transfer of tebipenem into middle ear effusion conduces to the favorable clinical outcomes of tebipenem pivoxil in pediatric patients with acute otitis media

Tebipenem pivoxil, an oral carbapenem antibiotic for pediatric use, exhibits excellent clinical effects on acute otitis media (AOM). The present study was conducted to assess the pharmacokinetic profile of tebipenem in middle ear effusion and to examine the clinical efficacy of tebipenem pivoxil by calculating the values of the pharmacokinetic-pharmacodynamic parameters (AUC/MIC, C _max/MIC, and T > MIC) of tebipenem at the site of action. Twenty-three pediatric outpatients diagnosed with AOM were enrolled. Ear discharge or nasopharyngeal swabs collected before the onset of oral administration were used to conduct bacteriological examinations, and subjects were then treated by twice-a-day oral administration of tebipenem pivoxil 6 mg/kg. The clinical isolates of Streptococcus pneumoniae and Haemophilus influenzae were obtained from 10 and 19 pediatric patients (8 overlapped), respectively. On day 2 of administration, blood and middle ear effusion were collected from 20 pediatric patients to measure plasma and middle ear concentrations of tebipenem. Consequently, the C _max and the AUC_0–∞ in plasma were 5.3 ± 1.6 μg/ml (mean ± SD) and 7.9 ± 0.2 μg h/ml, respectively. The C _max in middle ear effusion of tebipenem was 1.2 ± 0.1 μg/ml, exceeding its MIC for these pathogens. The ratio of AUC_0–∞ in middle ear effusion to AUC_0–∞ in plasma was 0.36, showing the good transfer of tebipenem into the effusion; this result corroborated the known high rate of clinical efficacy of tebipenem pivoxil for patients with AOM and the low incidence of recurrence in them as manifested by the healing rate of 94.1 % (16/17).     

Using Monte Carlo simulation to determine optimal dosing regimen for cefetamet sodium for injection

The objective of the study was to use Monte Carlo simulation to determine the optimal treatment dosing regimen of the cefetamet sodium for injection by analysing the pharmacokinetics (PK) parameters in healthy Chinese volunteers, and antibacterial activity in vitro was also examined. A three-cross Latin square single-dose PK study was designed. Twelve healthy volunteers were randomized to receive 500, 1000, and 2000 mg of cefetamet sodium for IV infusion over 30 minutes in three periods sequentially; and the washout time in between periods was 3 days. The drug concentrations in plasma were analysed by high-performance liquid chromatography, and the PK parameters were calculated using DAS2.0 PK software. The peak concentrations (C_max) at 0.5 hours were 37.78±7.29, 76.18±12.81, and 149.32±29.94 mg/l, the areas under concentration–time curve (AUC_0–t) were 69.75±14.44, 139.06±22.62, and 278.54±53.12 mg h/l, and the elimination half-life (t_1/2) were 1.69±0.19, 1.69±0.27, and 1.81±0.23 hours for 500, 1000, and 2000 mg of cefetamet sodium for injection, respectively. The disposition of cefetamet was appear to fit a two-compartment model with linear kinetics. Antibacterial activity in vitro showed that most Gram-negative bacteria, including non-extended-spectrum beta-lactamases (ESBL)-producing Enterobacter, Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, were sensitive to cefetamet. The result of Monte Carlo simulation showed that the probability of target attainment for bactericidal response (%fT>MIC≧50%) for susceptible bacteria was reached at all three dosing regimens of 500 mg, q6h, 1000 and 2000 mg, q8h and q6h. Considering the efficacy, safety, and pharmacoeconomy comprehensively, we recommended the dosing regimen of 500 mg, q6h for further clinical treatment based on the principle of minimum daily dosage.     

替比培南酯有关物质的合成

为了完善与强化对替比培南酯原料药的质量控制,建立替比培南酯原料药的质量标准,从替比培南酯的合成路线入手,分析并合成其中可能存在的5种有关物质:P1、P2、P6、P8、P9,并经¹H NMR和MS确证。纯度经HPLC确证在95%以上。合成的有关物质可以作为替比培南酯药物质量控制的杂质对照品,该合成方法条件温和、原料易得、操作简单。     

Investigation of pneumonia-causing pathogenic organisms in children and the usefulness of tebipenem pivoxil for their treatment

We investigated the usefulness of the novel oral carbapenem antibiotic tebipenem pivoxil (TBPM-PI) for treating bacterial pneumonia in children. Sputum and nasopharyngeal swabs were collected simultaneously, and causative organisms were identified by conventional bacterial culture together with exhaustive bacterial and viral identification by real-time polymerase chain reaction (PCR). The subjects were eight patients diagnosed with mild or moderate pneumonia at Sotobo Children’s Clinic Outpatient Department between October 2006 and June 2007. TBPM-PI was administered at the recommended clinical dose of 4 mg/kg b.i.d. to five patients and at a high dose of 6 mg/kg b.i.d. to three patients. Sputum was collected from all patients, and 11 strains were detected from washed sputum culture. Causative organisms were mainly Streptococcus pneumoniae (3 strains) and Haemophilus influenzae (6 strains), and nasopharyngeal swabs showed the same organisms as coughed-up sputum. Real-time PCR for individual viruses and Mycoplasma pneumoniae identified four cases of only bacterial infection, one case of M. pneumoniae coinfection, two cases of viral coinfection, and one case of both viral and M. pneumoniae coinfection. The clinical results indicated efficacy in all patients, and causative organisms were 100% eliminated. In the four patients with only bacterial infection, the average fever of 38.9°C at the start of treatment normalized the following day, showing excellent efficacy. No clinically problematic adverse events occurred, and compliance was good. We consider that these cases provide valuable insights into the identity of pathogenic organisms of pneumonia in children and the possible role of TBPM-PI in outpatient treatment.     

《中国药典》2015年版盐酸头孢他美酯干混悬剂有关物质检查方法的商榷

目的：通过对2个厂家8批盐酸头孢他美酯干混悬剂的检验和进一步研究,对该品种有关物质项检查方法进行优化改进。方法：依据《中国药典》2015年版标准进行检验,延长检测时间并考察2个厂家辅料的干扰情况。结果：盐酸头孢他美酯干混悬剂标准中有关物质检查项,需要增加检测时间至主峰保留时间的5倍,对于辅料峰的扣除必要时应采用辅料对照实验进行。结论：建议修订盐酸头孢他美酯干混悬剂标准的有关物质项目,以利于更好地控制该药品质量。     

头孢地尼对细菌感染小鼠的体内抗菌作用

目的:探讨头孢地尼对郑州市分离的致病菌感染小鼠的体内抗菌作用。方法:以最小致死量(MLD)0.5 ml腹腔注射金黄色葡萄球菌、肺炎链球菌、肺炎克雷伯菌和大肠埃希菌感染小鼠,建立小鼠全身感染模型,灌胃以不同剂量的头孢地尼0.5 ml,以头孢妥仑匹酯为阳性对照,并以半数有效量(ED50)为观察指标,研究头孢地尼的体内抗菌活性。结果:头孢地尼对金黄色葡萄球菌、肺炎链球菌、肺炎克雷伯菌和大肠埃希杆菌的ED50分别为0.12、0.08、1.25、2.18 mg/kg,头孢妥仑匹酯对上述菌株的ED50值分别为16.7、19.5、7.12、1.65 mg/kg。结论:头孢地尼体内抗球菌的活性远高于头孢妥仑匹酯,但其对大肠埃希杆菌的活性低于头孢妥仑匹酯,提示头孢地尼具有较优的抗球菌作用。