Clinical evaluation of S6472 (prolonged action preparation of cefaclor) in the treatment of skin and soft tissue infections. A double blind comparison of S6472 and cefaclor

A double-blind comparative study of S6472 and cefaclor (CCL) was conducted to evaluate the therapeutic efficacy, safety and usefulness in the treatment of skin and soft tissue infections. Either 750 mg b.i.d. of S6472 or 750 mg t.i.d. of CCL was administered orally to patients for a period of 7 consecutive days. Of the 250 cases (123 cases of S6472 group and 127 cases of CCL group) recruited in this trial, 228 cases (114 cases of S6472 and 114 cases of CCL) were adopted by the committee members for the evaluation of therapeutic efficacy, 238 cases (118 cases of S6472 group and 120 cases of CCL group) for usefulness, and 245 cases (121 cases of S6472 group and 124 cases of CCL group) were adopted for the evaluation of side effects. The backgrounds of both patients group were almost similar. The results obtained were as follows: Overall clinical effectiveness Of the 114 patients treated with S6472, excellent clinical responses were obtained in 11 patients, good in 79, fair in 19, poor in 5 (efficacy rate 78.9%), and of the 114 patients treated with CCL, excellent were in 16, good in 78, fair in 13, poor in 7 (efficacy rate 82.5%). There was no statistically significant difference between the 2 groups. Clinical effectiveness classified by initial severity and bacteriological efficacy There was no significant difference between the 2 groups in the clinical effectiveness classified by initial severity and in the bacteriological efficacy. Side effects were noticed in 5 patients of 121 treated with S6472 (4.1%) and in 2 patients of 124 treated with CCL (1.6%), and other 13 patients developed some abnormal laboratory findings. But these undesirable reactions were mild, and developed no significant difference between the 2 groups in the incidence of side effects. There was no significant difference between the 2 groups in the usefulness of the drugs. Conclusively, 750 mg b.i.d. of S6472 is anticipative of the same clinical efficacy, safety and usefulness as compared with that of 750 mg t.i.d. of CCL in the treatment of skin and soft tissue infections.     

A double-blind comparative study of S 6472 (a long-acting cefaclor) versus a conventional cefaclor preparation in complicated urinary tract infections

For an objective evaluation of the clinical efficacy, safety and usefulness of S 6472 (a long acting cefaclor) in non-catheterized patients with complicated urinary tract infections, a double-blind comparative study was performed using conventional cefaclor preparation (hereafter, CCL) as the control drug. S 6472 was administered orally at a single dose of 750 mg twice daily, and CCL at a single dose of 500 mg 3 time daily. The duration of the treatment was 5 days for either drug. Clinical efficacies were evaluated according to the criteria for evaluation of drug efficacy by the Japanese UTI Committee (3rd edition), and the following results were obtained. 1. The initial distribution of the patients' background characteristics was not significantly different between the S 6472 and CCL groups. 2. The overall clinical efficacy rates were 76.2% in the S 6472 group and 75.5% in the CCL group, indicating no significant difference between the 2 groups. When clinical efficacies evaluated according to different types of infections (UTI groups), the differences between the 2 drug groups were not significant in any of disease groups 2, 3, 4, and 6. 3. Clinical efficacy rates as evaluated by attending physicians were not significantly different between the 2 groups, either. 4. Bacteriological responses were evaluated as eradicated in 81.2% in the S 6472 group and 78.3% in the CCL group, suggesting no statistically significant difference. 5. The incidences of side effects were 2.9% (4/139) in the S 6472 group and 0.7% (1/141) in the CCL group, thus no significant differences existed between the 2 groups. On laboratory examination, 4 and 5 abnormal test values, respectively, were detected in 3/94 patients in the S 6472 group and 5/100 patients in the CCL group, but the difference was not significant between the 2 groups, either. All of these side effect symptoms and abnormal laboratory test values were mild in severity and transient. The results of the overall safety rating which was based on the evaluations of the side effects and laboratory test values indicated no significant difference between the 2 groups. 6. According to judgement by the attending doctors, the clinical usefulness rates evaluated based on the results of the efficacy and safety ratings were not significantly different between the S 6472 and CCL groups. These findings suggest that S 6472 produces excellent therapeutic results in complicated UTI patients without indwelling catheters and its clinical efficacy, safety, and usefulness are equal to those of the conventional CCL.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical evaluation of S 6472 granule preparation (sustained-release cefaclor) in chronic bronchitis

The S 6472 granule preparation (sustained-release cefaclor preparation) was administered to 15 cases of chronic bronchitis for its clinical evaluation; a daily dosage of 750 mg was orally given in 2 divided doses after breakfast and dinner for a duration of 7 to 22 days. Clinical effects were good in 11 cases, fair in 1 case and poor in 3 cases. Among the 13 cases other than 2 unadaptable Pseudomonas infections, good effectiveness was found in 11 cases (efficacy rate: 84.6%). There appeared to be no side effects or abnormal laboratory test values due to administration of this drug.     

高效毛细管电泳法测定头孢克洛干混悬剂中头孢克洛的含量

目的:测定头孢克洛干混悬剂中头孢克洛的含量.方法:采用高效毛细管电泳法.毛细管柱(60cm×75μm),运行缓冲液30mmol·L-1硼砂(pH 9.2),高压进样5s,分离电压12kV,温度为25℃,检测波长为254nm,地塞米松磷酸钠为内标.结果:头孢克洛在8～40μg·mL-1浓度范围内线性关系良好(r=0.999 8),平均回收率为 99.18% (n=5,RSD=1.69%).结论:本法简单、快捷、灵敏.     

Fundamental and clinical studies of a sustained release preparation of cefaclor in the surgical field

Fundamental and clinical studies of S6472 (sustained release preparation of cefaclor (CCL] were conducted in the surgical field and it was confirmed that the preparation is a useful drug. The following is the summary of the results from the fundamental and clinical studies: In vitro antibacterial activity. CCL showed MICs of 0.78 to 6.25 micrograms/ml against almost strains of S. aureus, E. coli and Klebsiella isolated from surgical wound regions, and the antibacterial activities were stronger than those of cephalexin (CEX). Clinical efficacy. S6472 was orally administered to 33 patients with skin and soft tissue infections in 2 divided doses. As a result, excellent clinical response was observed in 13 patients, good response observed in 14 patients, fair in 4 and poor in 1. The clinical efficacy in 1 of the 33 patients was unknown. Overall clinical effective rate was 84.4%. Adverse reaction. In 2 patients, mild gastrointestinal symptoms were observed.     

A clinical study on S6472, sustained release preparation of cefaclor, dermatological area

We conducted a clinical investigation on the use of S6472, an sustained release preparation of cefaclor, in the dermatological area. Thirty-two patients serving as subjects were divided into group I (14 cases, including folliculitis and acne pustulora), group II (16 cases, including furuncle, furunculosis and carbuncle) and others (2 cases). One or 2 wrappers (375 or 750 mg) of S6472 were orally administered to patients twice daily after meals. In group I, the efficacy rate was 100%. Clinical results were as follows: Excellent (6 cases), good (8 cases), fair (0), and poor (0). In group II, the efficacy rate was 93.8%: Excellent (10 cases), good (5 cases), fair (1 case), and poor (0). A decrease of the bacteriological effect was observed in 1 case with Staphylococcus epidermidis. A superinfection was noted in 1 case Staphylococcus aureus. The causative bacteria were all eradicated in the remaining 24 cases. No side effects were detected. From the above results, S6472 appears to be a useful preparation, twice daily oral administration has excellent effects against dermatological infections.     

Clinical evaluation of sustained release preparations of cefaclor in dental infections. Comparative double blind clinical studies of sustained release preparations with a regular preparation of cefaclor

In vitro viable cell count studies of sustained release preparations of cefaclor (CCL) conclude that the mixture of nonenteric and enteric coated granules of CCL in the ratio of 4 to 6 is the most appropriate form (4:6 form) for the sustained release preparation of CCL. In order to clinically confirm the above conclusion, comparative double blind clinical studies of 3 mixtures forms (2:8, 4:6 and 6:4 forms) with a regular preparation (CCL form) were conducted in dental infections regarding efficacy, safety, and usefulness of the 4 forms. Evaluable cases for efficacy and usefulness were 364 in total (96 cases for the 2:8 form group, 89 cases for the 4:6 form group, 89 cases for the 6:4 form group, and 90 cases for the CCL form group). Evaluable cases for safety were 404 cases in total (102 for the 2:8 form, 100 for the 4:6 form, 102 for the 6:4 form, and 100 for the CCL form). Daily dose of the 3 forms of sustained release preparations was 375 mg b.i.d. after breakfast and dinner and that of the CCL form 250 mg t.i.d. after breakfast, lunch and dinner. Following are the results of the clinical studies: There were no significant differences among the 4 patient-groups (2:8 form, 4:6 form, 6:4 form, and CCL form) regarding background factors of the patients and findings of their subjective and objective symptoms before the initiation of the administration, and it was therefore confirmed that there were no problems in conducting the comparative double blind clinical studies. Overall clinical effective rate determined by the efficacy evaluation criteria of the Japanese society of oral surgery (JSOS) were 89.5% at day 3 and 94.8% at day 5 in the 2:8 form group, 87.4% at day 3 and 95.5% at day 5 in the 4:6 form group, 86.4% at day 3 and 91.0% at day 5 in the 6:4 form group, and 93.3% at day 3 and 96.7% at day 5 in the CCL form group. The effective rate determined by the physicians who actually treated the patients were 84.4% in the 2:8 form group, 87.6% in the 4:6 form group, 84.1% in the 6:4 form group, and 87.8% in the CCL form group. In both judgments by the efficacy evaluation criteria of JSOS and the physicians, there were no significant differences among the 4 forms regarding overall clinical efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)     

抗感染药头孢克洛缓释胶囊

背景:20世纪60～70年代日本临床药学专家藤博发现,某些抗生素在体内的杀菌作用,主要取决于血与组织中药物浓度超过致病菌最低抑茵浓度(MIC)的时间(TMIC),而与药物浓度峰值关系不大,即杀菌效果和速度受药物接触时间的影响要大于其受药物浓度的影响.这类抗生素称为时间依赖性抗生素,如β-内酰胺类抗生素、大环内酯类(阿奇霉素除外)和克林霉素等.     

Clinical study of S 6472 granule preparation (sustained-release cefaclor) in chronic respiratory airway infections

S 6472 granule preparation, a sustained-release preparation of cefaclor, was administered to 21 patients with chronic respiratory airway infections for its clinical study; a daily dosage between 750 and 1,500 mg was orally given in 2 divided doses after breakfast and dinner for a duration of 3 to 14 days. Clinical effects were good in 15 cases, fair in 1 case, poor in 4 cases and unknown in 1 case. No side effects were observed except for a case of impaired appetite. There appeared to be no abnormal laboratory test valued due to the drug.     

Prolonged action potential duration of guinea-pig heart muscle after pethidine

Since recent experiments indicated class III antiarrhythmic properties of pethidine in vitro, we studied cardiac effects of pethidine in vivo. Monophasic action potentials at different pacing rates were recorded from the left ventricular epicardium of pentobarbital anaesthetized guinea-pigs by means of suction electrode catheter. Intravenous injection of pethidine 2 mg/kg prolonged the action potential duration, and increased left ventricular developed pressure and dP/dt max, compared to animals receiving saline only. It is concluded that pethidine appears to have class III antiarrhythmic properties.     

Clinical studies on S 6472 granule preparation (sustained-release cefaclor) in chronic respiratory tract infections

S 6472 granule preparation (sustained-release cefaclor) was orally administered to 15 patients with chronic respiratory tract infections (2 acutely exacerbated cases of chronic bronchitis, 13 cases of secondary infections consisting of 1 case of bronchial asthma, 2 cases of bronchial asthma/pulmonary emphysema, and 10 cases of bronchiectasis) at a daily dose of 750 mg divided into 2 doses administered after breakfast and dinner, for a duration of 14 days. The drug was ineffective in 3 of the 10 cases of bronchiectasis but was effective in the other 12 cases, with a rate of efficacy of 80%. There were no side effects of abnormal laboratory findings due to administration of this drug.     

Fundamental and clinical studies of S 6472 (sustained release preparation of cefaclor) in the pediatric field

Fundamental and clinical studies on S 6472 were carried out and following results were obtained. Serum concentrations after single oral administration showed 2 peaks at 1 or 2 hours and 5 or 6 hours in the cases with normal meal. Namely this drug has much more maintenance of serum concentration than normal cefaclor. In maintenance of serum concentrations after the administration, there were no obviously difference between normal and heavy meal. S 6472 was administered twice a day to 7 patients with various infections (bronchopneumonia 2 cases, acute bronchitis 1 case, purulent tonsillitis 4 cases) and clinical responses were all effective results. Pathogenic bacteria of S. aureus, S. pneumoniae, S. pyogenes and H. influenzae were completely eliminated in all cases. No significant side effects were observed. On the above results, this administration method of S 6472 twice a day was considered to be good response against mild or moderate bacterial infections in children.     

Myelotoxic action of the new antitumor preparation spirobramin

Experiments on 110 white noninbred tumor-free rats were made to explore the myelotoxic action of a new antineoplastic drug spirobramine. A single (200 mg/kg) intravenous injection and a course of drug treatment (40 mg/kg 5 times every other day) produced monotypic changes in the peripheral blood and bone marrow hemopoiesis, primarily marked by inhibition of erythroid, eosinophilic and thrombocytic myeloid fibers followed by the development of moderate anemia, thrombocytopenia and aneosinophilia in the peripheral blood. A single injection of spirabramine in an MTD produced more pronounced changes in the blood than injection of the drug in divided doses.     

Prolonged action of deamino-carba analogues of oxytocin on the rat uterus in vivo

Deamino-oxytocin and some of its ‘carba’ analogues have a protracted effect on the rat uterus in vivo. Comparison of the elimination constants of the individual analogues of oxytocin and of deamino-oxytocin shows that the lower elimination rate of the analogues depends on the absence of the amino group in position 1 of the peptide chain. The individual modifications of the disulphide bridge influence the value of the elimination constants in different ways. Only the modification of hemicystine in position 6 of deamino-oxytocin resulted in an analogue with an even more prolonged action. The analogues with the most protracted action on the uterus, i.e. deamino-dicarba-oxytocin and deamino-6-carba-oxytocin, had a shorter antidiuretic action than oxytocin.     

头孢克洛颗粒体外溶出度的测定

目的建立头孢克洛颗粒的体外溶出度测定方法。方法紫外分光光度法测定头孢克洛颗粒的溶出度,以水（37℃）为溶出介质,以浆法（50r·min^-1）为溶出方法,在264nm测定头孢克洛的溶出度。结果根据上述条件建立头孢克洛颗粒剂的溶出度测定方法。结论所建立的头孢克洛颗粒剂溶出度检查方法可供应用或作为修订标准的参考。     

反相高效液相色谱法分析测定头孢克洛

以磷酸盐缓冲液－甲醇为流动相在Ｃ１８柱上分离测定头孢克洛，检测波长２５４ｎｍ，乙酰苯胺作内标。ＣＣＬ进样量在０．４－２．４μｇ间线性关系良好，加样回收率９９．８％，重复进样的ＲＳＤ为０．３６％。     

不同剂量丙磺舒对头孢克罗药物动力学的影响

目的 :观察不同剂量丙磺舒 (Pro)对头孢克罗 (Cef)药动学的影响 ,为两者联用提供依据。方法 :家兔 30只随机分成 5组 ;Cef 5 0mg·kg- 1组 ,Cef5 0mg·kg- 1+Pro 5 0mg·kg- 1组 ,Cef 5 0mg·kg- 1+Pro 10 0mg·kg- 1组 ,Cef 5 0mg·kg- 1+Pro2 0 0mg·kg- 1组 ,Cef 2 5mg·kg- 1+Pro 10 0mg·kg- 1组。灌胃给药后于不同时间股静脉取血 ,HPLC法测定Cef血药浓度 ,NDST程序计算药动学参数。结果 :在给予Cef 5 0mg·kg- 1条件下 ,随Pro联用剂量的增大 ,Cef的Cmax、AUC增高而Cl/F、V/F减少 ;Cef2 5mg·kg- 1+Pro 10 0mg·kg- 1组各参数 (除Cl/F外 )与Cef 5 0mg·kg- 1组差异不显著。结论 :Pro可明显改变Cef的药动学 ,在实验剂量范围内其影响程度与丙磺舒剂量有关。Cef 2 5mg·kg- 1联用Pro10 0mg·kg- 1可产生Cef 5 0mg·kg- 1的血药水平。