• YAKHAK HOEJI
• /
• v.42 no.3
• /
• pp.284-289
• /
• 1998

The effect of reaction condition, solvent addition and thermal treatment on the bulk density, crystallinity and chemical properties of the freeze-dried cefazohn sodium was inves tigated to prepare the cefazolin sodium powder for injection with good flowability. Crystalline cefazolin sodium powder with high untapped-bulk density (about 45%) and low compressibility (about 40%) was obtained by solvent addition to the very highly concentrated cefazohn sodium solution followed by subsequent thermal treatment before freeze-drying. The desirable solvent was low substituted alcohol such as isopropyl alcohol and anhydrous ethanol with the final concentration of about 9%. The pH adjustment and nitrogen gas purging during the reaction did not give significant effect on the chemical properties such as content, color, transmittance and pH of the reconstituted cefazolin sodium aqueous solution.

• YAKHAK HOEJI
• /
• v.40 no.3
• /
• pp.306-310
• /
• 1996

Five pseudopolymorphic modifications of cefazolin sodium were prepared by recrystallization. They were characterized by DSC and TGA. The solubilities of all modifications were c hecked through the dissolution test.

• Journal of Pharmaceutical Investigation
• /
• v.22 no.2
• /
• pp.139-148
• /
• 1992

A prodrug of cefazolin pivaloyloxymethyl ester (CFZ-PV) was synthesized to improve oral absorption and bioavailability of parent drug by esterification of sodium cefazolin (CFZ) with chloromethyl pivalate. The successful synthesis of CFZ-PV was confirmed by spectroscopic analysis. Partition coefficient studies showed that CFZ-PV is more lipophilic than CFZ. The pharmacokinetic characteristics of CFZ-PV and CFZ preparations were compared following oral administrations of these compounds to rabbits. The analysis of CFZ in plasma was conducted by HPLC method. The ester compound (prod rug) was not detected in plasma following oral administration of CFZ-PV, and although CFZ-PV had not microbiological activity in vitro, the plasma taken after CFZ-PV administration had microbiological activity. From above observations, it was noted that CFZ-PV is rapidly hydrolyzed to CFZ in the body. And it was found that the oral absorption of CFZ-PV was increased, yielding 2-fold higher bioavailability than CFZ. From the results of this experiment, it was concluded that CFZ-PV could be a novel prodrug of CFZ which can improve the oral bioavailability of CFZ.

• Journal of Pharmaceutical Investigation
• /
• v.24 no.4
• /
• pp.265-271
• /
• 1994

Cefazolin ethoxycarbonylethyl ester (CFZ-ET) was synthesized to improve oral absorption and bioavailability of the parent drug by esterification of sodium cefazolin (CFZ-Na). The successful synthesis of CFZ-ET was identified with analysis of UV spectra, FT-lR spectra and NMR spectra. Partition coefficient studies showed that CFZ-ET was more lipophilic than CFZ-Na and the ester was hydrolyzed into the parent drug in vivo. Although CFZ-ET did not have antimicrobial activity in vitro, the plasma taken after the oral administration of CFZ-ET had antimicrobial activity. Based on above observations, CFZ-ET might be rapidly hydrolyzed to CFZ in the body. Therefore, it may be concluded that CFZ-ET could be a novel prodrug of CFZ which can improve the bioavailability of CFZ-Na.

• Journal of Pharmaceutical Investigation
• /
• v.16 no.2
• /
• pp.85-88
• /
• 1986

To estimate the effect of some injectable antibiotics (ampicillin sodium, cefazolin sodium, cephaloridine, cefuroxime sodium and chloramphenicol sodium succinate) on pyrogen tests, the Limulus amebocyte lysate (LAL) test and an ultrafiltration technique were used. The rabbit pyrogen test was also used in the case of cafazolin sodium. At high antibiotic concentrations, these samples which were artificially contaminated with endotoxin inhibited the gelation reaction of LAL. But the gelation reaction occurred when most of the antibiotic was removed by ultrafiltration. Likewise, cefazolin sodium interfered not only with the LAL test but also with the rabbit pyrogen test. From these results it can be said that special modification to eliminate interference should be taken into consideration for valid method of pyrogen tests in the parenteral products containing these antibiotics.

• Korean Journal of Clinical Pharmacy
• /
• v.3 no.1
• /
• pp.61-70
• /
• 1993

A new cephalosporin derivate, cefazolin phthalidyl ester(CFZ-PT) was synthesized to improve oral absorption and bioavailability of parent drug by esterification of sodium cefazolin(CFZ). Partition coefficient studies showed that CFZ-PR is more lipophilic than CFZ. The pharmacokinetic characteristics of CFZ-PT and CFZ preparations were compared following oral administrations of these compounds to rabbits. The analysis of CFZ in plasma was conducted by HPLC method. The ester compound was not detected in plasma following oral administration of CFZ-PT was increased by yielding 3.5-fold bioavailability rather than CFZ. From the results of this experiment, it was concluded that CFZ-PT could be a novel prodrug of CFZ which can improve the oral bioavailability of CFZ.

• Journal of Pharmaceutical Investigation
• /
• v.23 no.2
• /
• pp.61-69
• /
• 1993

Prodrug of cefazolin (CFZ) was prepared with the objective of improving its oral bioavailability. Cefazolin phthalidyl ester (CFZ-PT) was synthesized and evaluated as potential prodrug form. The successful synthesis of CFZ-PT was identified by spectroscopic analysis. Partition coefficient studies showed that CFZ-PT is more lipophilic than CFZ and the ester was hydrolyzed enzymatically into the parent drug in blood, liver and intestinal homogenates. The pharmacokinetic characteristics of CFZ-PT and CFZ were compared following oral administrations to rabbits. Serum CFZ concentration was determined by HPLC method and the ester compound (prodrug) was not detected in serum following oral administration of CFZ-PT. CFZ-PT did not have antimicrobial activity in vitro against Bacillus subtilis ATCC 6633, whereas CFZ-PT in serum after oral administration to rabbits had antimicrobial activity. From above observations, it was noted that CFZ-PT is rapidly hydrolyzed to CFZ in the body and the bioavailability of CFZ-PT was increased by 3.5-fold than that of CFZ. From these results of this study, it was concluded that CFZ-PT may be a novel prodrug of CFZ which can improve the oral absorption of CFZ.

• Korean Journal of Veterinary Service
• /
• v.22 no.1
• /
• pp.85-92
• /
• 1999

This study was investigated resistance on disinfectants and antibiotics of Clostridium chauvoei isolated from dairy farm in Kyongbuk province. The results obtained were summarized as follows ; C chauvoei isolated from dairy farm were susceptible to norfloxacin, penicillin, tetracycline, erythromycin, enrofloxacin, bacitracin, tyrosine, cephalothin and cefazolin but resistant to gentamicin, kanamycin, sulfamethoxazole＋trimethoprim, amikacin, neomycin streptomycin, colistin. In effect on disinfectants, C chauvoei was inhibited completely to growth in mercuric bichloride ($HgCl_2$), harasol(sodium hypochloride 4-6%), long-life(high boiling tar acids et al), and phenol($C_6$$H_5$OH), but growth in all-stop(didecyl dimethyl ammonium chloride 10%), powercide(potassium monopersulphate 50% et al), antec vercon-s(triple salt 50% et al), and taego-51(6-alkyl-2.6-diaza-hexane-carbonic acid-1ㆍHCl et al). The effect of disinfectant was excellent in mercuric bichloride and harasol.

• Journal of Applied Biological Chemistry
• /
• v.58 no.3
• /
• pp.227-232
• /
• 2015

A microarray study has been employed to understand changes of gene expression in E. coli KD43162 resistant to ampicillin, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, cefazolin, cefepime, aztreonam, imipenem, meropenem, gentamicin, tobramycin, ciprofloxacin, levofloxacin, moxifloxacin, fosfomycin, and trimethoprim-sulfamethoxazole except for amikacin using disk diffusion assay. Using Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and MALDI-TOF MS analyses, 36 kDa of outer membrane proteins (OMPs) was found to be deleted in the multidrug resistant E. coli KD 43162. Microarray analysis was used to determine up- and down-regulated genes in relation to multidrug resistant E. coli KD43162. Among the up-regulated genes, these genes were corresponded to express the proteins as penicillin-binding proteins (PBPs), tartronate semialdehyde reductase, ethanolamine utilization protein, shikimate kinase I, allantoinase, predicted SAM-dependent methyltransferase, L-glutamine: D-fructose-6-phosphate aminotransferase (GFAT), phospho-glucosamine mutase, predicted N-acetylmannosamine kinase, and predicted N-acetylmannosamine-6-P epimerase. Up-regulation of PBPs, one of primary target sites of antibiotics, might be responsible for the multidrug resistance in E. coli with increasing amount of target sites. Up-regulation of GFAT enzyme may be related to the up-regulation of PBPs because GFAT produces N-acetylglucosamine, a precursor of peptidoglycans. One of GFAT inhibitors, azaserine, showed a potent inhibition on the growth of E. coli KD43162. In conclusion, up-regulation of PBPs and GFATs with the loss of 36 kDa OMP refers the multidrug resistance in E. coli KD 43162.