头孢美唑与四种注射液的配伍实验

采用紫外分光光度法测定了头孢美唑与四种注射液（即维生素Ｃ、维生素Ｂ６、氨甲苯酸、酚磺乙胺）配伍后的含量并进行了外观观察、ｐＨ值测量，考察有无配伍变化。结果表明：头孢美唑与维生素Ｃ、氨甲苯酸注射液配伍，在低于３７℃时４ｈ内稳定，头孢美唑与维生素Ｄ６、酚磺乙胺注射液配伍，在低于３７℃时６ｈ内稳定。     

头孢美唑与四种注射液的配伍实验

采用紫外分光光度法测定了头孢美唑与四种注射（即维生素Ｃ，维生素Ｂ２，氨甲苯酸，酚磺乙胺）配伍后的含量并进行了外观观察，ｐＨ值测量，考察有无配伍变化，结果表明：头孢美唑与维生素Ｃ，氨甲苯酸注射液配伍，在低于３７℃时４ｈ内稳定，头孢美唑与维生素Ｂ６，酚磺乙胺注射液配伍，在低于３７℃时６ｈ内稳定。     

盐酸洛美沙星注射液与2种药物配伍的稳定性

目的：在４℃、２５℃,３７℃下考察止血敏、维生素Ｃ分别与沙星注射液配伍稳定性。方法Ｌ：采用双波长分光光度法测定各配伍液中各自的含量变化情况。结果：本伍在上述各上,０￣６ｈ内其外观、突起琢呈均无明显变化。     

头孢他定与4种注射液在输液中的配伍试验

本文采用反相高效液相色谱法，考察了头孢他定和４种临床常用药物在输液中配伍的稳定性。结果表明，在室温（２３℃）下，头孢他定与维生素Ｃ、维生素Ｂ６、地塞米松磷酸钠、氯化钾注射液在５％葡萄糖氯化钠注射液中配伍稳定，７ｈ内配伍液ｐＨ值及头孢他定的含量均变化不大，且外观无改变。     

甲硝唑葡萄糖注射液与地塞米松磷酸钠注射液的配伍稳定性

本文报告了甲硝唑葡萄糖注射液与地塞米松磷酸钠注射液配伍稳定性实验。结果表明：在室温条件下（２０℃），两 药配伍后６ｈ内外以、ＰＨ值、紫外光谱及紫外法和ＨＰＬＣ法所测含量均未发生明显改变。     

地塞米松磷酸钠注射液和维生素B6注射液的配伍稳定性

地塞米松磷酸钠注射液与维生素Ｂ６注射液在５％葡萄注射液中配伍后６ｈ内，外观，ＰＨ值、薄层Ｒｆ值及含量测定无显著；薄层层析实验证明二者在５％葡萄糖中配伍可行。     

注射用异环磷酰胺与5种输液配伍的稳定性考察

考察２５℃下２４ｈ,注射用异环磷酰胺与５种输液配伍的稳定性。方法：采用反相高效液相色谱法测定配伍后２４ｈ内不同时间异环磷酰胺的含量,同时观察外观并测定ｐＨ值。结果：２５℃、３５℃下２４ｈ内,配伍液的外观澄明无色变,未见气泡及沉淀,ｐＨ值及注射用异环磷酰胺含量均无明显变化。结论：２５℃及３５℃下２４ｈ内,注射用异环磷酰胺与５种输液可以配伍使用。     

头孢唑肟在输液中与6种注射剂配伍的稳定性研究

目的:研究头孢唑肟(Ceftizoxime ,CZX) 在5 % 葡萄糖输液中与维生素B₆ 等6 种注射剂配伍的稳定性,为临床合理用药提供科学依据。方法:选择在35 ℃下6h 内观察配伍液的外观,pH 及CZX 紫外光谱的变化。用紫外分光光度法测定CZX 的含量。结果:其稳定性与温度和pH 有关。结论:在35 ℃下6h 内与维生素B₆ 、地塞米松、酚磺乙胺、氯化钾注射剂配伍,则稳定可用;与维生素C、氨茶碱注射剂配伍,则最好在4h 内使用     

替硝唑葡萄糖注射液与注射用头孢噻肟钠的配伍稳定性

目的：考察４℃、２５℃、３７℃下２４ｈ内替硝唑葡萄糖注射液与注射用头孢噻肟钠的配伍稳定性。方法：采用反相高效液相色谱法测定配伍后４℃、２５℃、３７℃下２４ｈ内不同时间替硝唑与头孢噻肟钠的含量,同时观察外观并测定ｐＨ值。结果：在３种温度下２４ｈ内,配伍液的 ｐＨ值无明显变化;配伍液的外观、替硝唑和头孢噻肟钠的含量随时间有明显变化;在 ４℃ ６ｈ时、２５℃２ｈ时、３７℃１ｈ时,配伍液的吸收曲线发生微小变化,产生了新的最大吸收峰位。结论：在４℃ ６ｈ内、２５℃２ｈ内、３７℃１ｈ内,替硝唑葡萄糖注射液与注射用头孢噻肟钠的配伍液稳定。     

头孢氨噻肟与4种注射液在输液中的配伍试验

采用反相高效液相色谱法，考察了头孢氨噻肟和４种临床常用药物在输液中配伍的稳定性。结果表明，在室温下，头孢氨噻肟与维生素Ｃ，维生素Ｂ６，地塞米松磷酸钠，氯化钾注射液在５％葡萄糖氧化钠注射液中配伍稳定，７ｈ内配伍液ｐＨ值及头孢氨噻肟的含量变化不大，且外观无改变。     

Studies of ceftizoxime in perinatal period

Bacteriological studies and clinical evaluations of ceftizoxime (CZX) in perinatal period were carried out, and results are summarised as follows: Antibacterial activities of CZX in amniotic fluid were determined using the broth dilution method, and bactericidal effect on Streptococcus agalactiae, Staphylococcus aureus and Escherichia coli were demonstrated. The bactericidal effect of CZX increased in amniotic fluid and remarkable increases of activities against resistant strains were demonstrated. The penetration of CZX into mother's milk was low, and it was speculated that the drug transfer to the newborn through breast feeding was very little. Clinically, CZX was effective in the treatment of perinatal infections without any side effect. The above results has demonstrated that CZX is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.     

Therapeutic effect of ceftizoxime on infections in aged patients

Ceftizoxime (CZX) were administered and tested for the efficacy and safety in 80 elderly patients who were older than 65 years of age with infections. The sensitivity of bacteria found in these infections to CZX was examined before the administration of the drug. Serum concentrations and the rate of urinary output of the drug were examined in 3 cases. The clinical effect of CZX was as follows: 29 cases (36.3%) of excellent effectiveness and 31 cases (38.8%) showed moderate effectiveness. The patients were divided into 2 groups depending on the presence or the absence of other diseases in their backgrounds. Effectiveness of CZX for patients with and without other diseases were 74.0% and 85.7%, respectively. The effectiveness of CZX in patients with other diseases in their background was lower than the group without other diseases. Other antibiotics were used in 16 cases before the use of CZX. The effectiveness of CZX for these patients was 62.5%. Infecting bacteria were detected in a total of 46 cases (19 cases of respiratory infections and 27 cases of urinary tract infections). Among the respiratory cases, 8 were due to Gram-positive bacteria and 11 were due to Gram-negative bacteria. No Gram-positive organisms were detected from urinary tract infections, which were all due to Gram-negative bacteria. Sensitivities of isolates of these infecting bacteria to CZX were very sensitive 3 isolates, sensitive (++) 8 and slightly sensitive (+) 1 isolate. It was found that CZX was effective against 39 of 46 cases from which causative organisms were identified. The effectiveness ratio was 84.8%. Serum concentration of CZX was determined after a drip injection of 1 g CZX for 1 hour. The half-lives of CZX in plasma in healthy subjects and aged patients were 1.33 hours and 2.15 hours, respectively. The rate of urinary output of CZX during 6 hours after the injection was 76.4% in healthy subjects. Delayed urinary output which was 58.2% during 7 hours after injection was observed in aged patients. Fever in 1 patient and eosinophilia in 3 cases were observed after administration of CZX.     

Effect of 1-aminobenzotriazole on the in vitro metabolism and single-dose pharmacokinetics of chlorzoxazone, a selective CYP2E1 substrate in Wistar rats

The aim of this study was to study the effect of 1-aminobenzotriazole (ABT) on in vitro metabolism, oral, and intravenous (IV) pharmacokinetics of chlorzoxazone (CZX) in rats. Enzyme kinetics of CZX was performed with rat and human liver microsomes and pure isozyme (CYP2E1) with and without ABT. The enzyme kinetics (V(max) and K(m)) of the formation of 6-hydroxychlorzoxazone (OH-CZX) was found to be similar among rat liver microsomes (3486 pmol mg protein(-1) min(-1) and 345 microM), human liver microsomes (3194 pmol mg protein(-1) min(-1) and 335 microM) and pure isozyme (3423 pmol mg protein(-1) min(-1) and 403 microM), but K(I) and K(inact) values for ABT towards the ability to inhibit the formation of OH-CZX from CZX varied between liver microsomes (rat: 32.09 microM and 0.12 min(-1); human: 27.19 microM and 0.14 min(-1)) and pure isozyme (3.18 microM and 0.29 min(-1)). The novel robust analytical method was capable of quantifying CZX, OH-CZX, and ABT simultaneously in a single run, and the method was used for both in vitro and in vivo studies. Pre-treatment of rats with ABT prior to oral and IV administration of CZX significantly decreased the clearance (threefold) and consequently increased the AUC of CZX (approx. three- to fourfold). When rats were pre-treated with ABT, the formation of OH-CZX was completely blocked after oral and IV administration; however, we were able to measure OH-CZX in rats administered with CZX by oral and IV routes without pre-treatment of ABT. The oral bioavailability of CZX was approximately 71% when dosed alone and reached 100% under pre-treatment with ABT. The t(1/2) values of CZX was significantly prolonged for oral dosing compared with IV dosing under pre-treated conditions with ABT, suggesting an involvement of pre-systemic component in the disposition of CZX. The pharmacokinetic parameters of ABT did not change when it was dosed along with CZX (oral and IV), indicating that either CZX or OH-CZX had no effect on disposition of ABT. The plasma concentrations of ABT were above and beyond the required levels to inhibit CYP2E1 enzyme for at least 36 h post-treatment.     

Clinical laboratory approach for estimating effective administrative dose of ceftizoxime. Observation from MIC and ceftizoxime disc susceptibility test

In vitro activities of ceftizoxime (CZX) against 328 clinical isolates were determined using the agar dilution method at an inoculum level of 10(6) cfu/ml. CZX was highly active against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Proteus vulgaris with MIC values below 0.20 microgram/ml. It was also active against Serratia marcescens and Enterobacter aerogenes with MIC85 of 3.13 micrograms/ml. CZX was less active against Staphylococcus aureus and Staphylococcus epidermidis, showing inhibitory activities against only 47 and 78% of these clinical isolates, respectively, at a dose level of 12.5 micrograms/ml. CZX was not active against Pseudomonas aeruginosa and Enterococcus faecalis. The reliability of CZX disc diffusion susceptibility tests for quantitative estimation of antimicrobial activities was also investigated using 8 mm diameter discs (Showa) and 6 mm diameter discs (Eiken), both of which contained 30 micrograms/disc of CZX. These disc susceptibility test results were well correlated with MICs, hence the CZX disc susceptibility test should be useful for the estimation of proper dose levels of CZX, except against P. aeruginosa and E. faecalis. For the interpretation of CZX disc tests, a 3 category system has been used in USA and Europe, but a 4 category system is generally used in Japan. The 3 category system uses break points to classify bacteria into 3 categories of susceptibility according to MIC values as follows: resistant (R) MIC greater than 32 micrograms/ml, moderately susceptible (MS) MIC 16-32 micrograms/ml, and susceptible (S) MIC less than or equal to 8 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

The concentration of ceftizoxime in serum and lung tissues and prophylaxis of postoperative infections

There are few clinical reports about the concentration of ceftizoxime (CZX) in lung tissues. At present, clinically, we report the concentration of the drug in serum and lung tissues on 26 cases of chest disease and an effect of the drug on prophylaxis of postoperative pulmonary infections. Our results are the following; The peak concentration of CZX in serum is 54.7 micrograms/ml at 1 hour after starting drip infusion of CZX 1 g. The serum half-life of CZX (beta phase) is 2.07 hours. The concentration of CZX in lung tissues is from 43.6 to 78.7% of serum level. CZX is useful to prophylaxis of postoperative infections after thoracotomy, especially in case of administration of CZX 1 g just before operation. Eruption was found in 1 of 26 cases. However, no side effects of the drug are noticed in other 25 cases.     

Time‐dependent effects of Klebsiella pneumoniae endotoxin on the pharmacokinetics of chlorzoxazone and its main metabolite, 6‐hydroxychlorzoxazone,in rats: restoration of the parameters in 96 hour in KPLPS rats to control levels

It has been reported that chlorzoxazone (CZX) was primarily metabolized via hepatic Cyp2e1 to form 6‐hydroxychlorzoxazone (OH‐CZX) in rats, and the activity of aniline hydroxylase (a Cyp2e1 marker) in the liver was significantly decreased in rats at 24 h after pretreatment with lipopolysaccharide derived from Klebsiella pneumoniae (24 h KPLPS rats), whereas the levels were not changed at 2 h and 96 h in the KPLPS rats. Thus, the time‐dependent pharmacokinetic parameters of CZX and OH‐CZX were evaluated after the intravenous administration of CZX (20 mg/kg) to control rats, and the 2 h, 24 h and 96 h KPLPS rats along with the time‐dependent changes in the protein expression of hepatic Cyp2e1. After the intravenous administration of CZX to 24 h KPLPS rats, the AUC_{0–2 h} of OH‐CZX and AUC_{OH‐CZX, 0–2 h}/AUC_CZX were significantly smaller (by 40.5% and 71.2%, respectively) than those of controls due to the significant decrease (by 75.3%) in the protein expression of hepatic Cyp2e1. However, in 96 h KPLPS rats, the pharmacokinetic parameters of both CZX and OH‐CZX were unchanged compared with controls due to the restoration of the protein expression of hepatic Cyp2e1 to control levels. These observations highlighted the existence of the time‐dependent effects of KPLPS on the pharmacokinetics of CZX and OH‐CZX in rats. Copyright © 2009 John Wiley & Sons, Ltd.     

Hepatic disposition of the cytochrome P450 2E1 marker chlorzoxazone and its hydroxylated metabolite in isolated perfused rat livers

The steady-state disposition of chlorzoxazone (CZX) and its hydroxylated metabolite 6-hydroxychlorzoxazone (HCZX) was determined in a single-pass isolated perfused rat liver (IPRL) model using constant CZX concentrations of 10-200 microM. The concentrations of CZX, HCZX, and/or HCZX glucuronide in the perfusate, bile, and liver tissues were measured and kinetic parameters calculated. Upon an increase in CZX inlet concentrations from 10 to 200 microM, its extraction ratio sharply declined from 0.681 to 0.087. This was associated with a saturable formation of HCZX, which was rapidly and completely metabolized to its glucuronide conjugate. Whereas the biliary excretion of CZX was negligible, that of HCZX was substantial (up to 40% of the generated metabolite). Overall, 79-93% of the CZX dose (10-200 microM) was recovered in our model as CZX and HCZX. Additionally, HCZX accounted for 56% (200 microM) to 71% (10 microM) of the extracted CZX dose. Further, a preliminary study using the preformed HCZX showed a complete (100%) recovery of the metabolite as its conjugate. Therefore, the unrecovered portion of CZX dose in our study (7-21% of the administered dose or 29-44% of the extracted dose at inlet CZX concentrations of 10-200 microM) is most likely due to parallel metabolism of CZX to other metabolites.     

A fundamental and clinical study of ceftizoxime in the field of obstetrics and gynecology (author's transl)

A fundamental and clinical study of ceftizoxime (CZX), a new cephalosporin antibiotic, has brought about the following results. 1. The antibacterial activity of CZX against Bacteriodes fragilis and B. thetaiotaomicron was superior to that of CEZ, but inferior to that of CFX. CZX was the most active of the 3 drugs against B. distasonis, and was as active as CFX against B. vulgatus. The MICs of CZX against Peptococcus, Peptostreptococcus and anaerobic Streptococcus were 1.56 microgram/ml or lower. CEZ was more active than CZX against these anaerobic cocci. 2. The concentrations of CZX in female genital organs and retroperitoneal dead space exudate after drip infusion of 1 g were high enough to fulfill the MICs of many bacterial isolates. 3. CZX administered intravenously to 9 patients in daily doses of 1 approximately 8 g for 4 approximately 11 days was 100% effective. Pathogenic bacteria in 6 of the patients were eradicated in 4 and partially eradicated in 1. The other patient had no bacteriological examination after therapy. 4. No adverse reaction was observed. From above results it is concluded that CZX must be one of the most effective antibiotics for the treatment of gynecological infections.     

Effect of 1-aminobenzotriazole on the in vitro metabolism and single-dose pharmacokinetics of chlorzoxazone,a selective CYP2E1 substrate in Wistar rats

The aim of this study was to study the effect of 1-aminobenzotriazole (ABT) on in vitro metabolism, oral, and intravenous (IV) pharmacokinetics of chlorzoxazone (CZX) in rats. Enzyme kinetics of CZX was performed with rat and human liver microsomes and pure isozyme (CYP2E1) with and without ABT. The enzyme kinetics (V_max and K_m) of the formation of 6-hydroxychlorzoxazone (OH-CZX) was found to be similar among rat liver microsomes (3486?pmol?mg?protein^?1?min^?1 and 345?µM), human liver microsomes (3194?pmol?mg?protein^?1?min^?1 and 335?µM) and pure isozyme (3423?pmol?mg?protein^?1?min^?1 and 403?µM), but K_I and K_inact values for ABT towards the ability to inhibit the formation of OH-CZX from CZX varied between liver microsomes (rat: 32.09?µM and 0.12?min^?1; human: 27.19?µM and 0.14?min^?1) and pure isozyme (3.18?µM and 0.29?min^?1). The novel robust analytical method was capable of quantifying CZX, OH-CZX, and ABT simultaneously in a single run, and the method was used for both in vitro and in vivo studies. Pre-treatment of rats with ABT prior to oral and IV administration of CZX significantly decreased the clearance (threefold) and consequently increased the AUC of CZX (approx. three- to fourfold). When rats were pre-treated with ABT, the formation of OH-CZX was completely blocked after oral and IV administration; however, we were able to measure OH-CZX in rats administered with CZX by oral and IV routes without pre-treatment of ABT. The oral bioavailability of CZX was ～71% when dosed alone and reached 100% under pre-treatment with ABT. The t_1/2 values of CZX was significantly prolonged for oral dosing compared with IV dosing under pre-treated conditions with ABT, suggesting an involvement of pre-systemic component in the disposition of CZX. The pharmacokinetic parameters of ABT did not change when it was dosed along with CZX (oral and IV), indicating that either CZX or OH-CZX had no effect on disposition of ABT. The plasma concentrations of ABT were above and beyond the required levels to inhibit CYP2E1 enzyme for at least 36?h post-treatment.     

Obesity-induced increase of CYP2E1 activity and its effect on disposition kinetics of chlorzoxazone in Zucker rats

This study was designed to investigate the induction of CYP2E1 in obese Zucker rats and its effect on the disposition kinetics of chlorzoxazone (CZX). CZX 20mg/kg was administered to three groups of rats: normal Zucker rats fed a normal diet (ND), normal Zucker rats fed a high-fat diet (HF), and genetically obese Zucker rats fed a normal diet (OB). The values of the area under the plasma concentration-time curve from 0 to infinity (AUC(infinity)) of CZX were in the order of ND>HF>OB rats. The AUC(infinity) values of total 6-hydroxychlorzoxazone (6OHCZX-T), which is considered to be a CYP2E1 metabolic marker, were in the opposite order. The values of the AUC(infinity) ratio (6OHCZX-T/CZX) in ND, HF and OB rats were approximately 0.2, 0.3 and 0.4, respectively. The CZX concentration in fat was much higher than the concentrations in plasma, liver and kidney in all groups. Induction of CYP2E1 protein was greater in both liver and fat of OB rats than in those of HF rats. Microsomal activity of CYP2E1 in liver and fat was also in the order of OB>HF>NM rats. These results suggest that CYP2E1 may be induced in liver and fat of obese patients, thereby potentially altering the disposition kinetics of not only CZX, but also other lipophilic drugs metabolized by CYP2E1.