• Archives of Pharmacal Research
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• v.23 no.3
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• pp.197-201
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• 2000

In an aqueous piperacillin sodium solution, a well-defined single wave or single peak was observed by direct current(DC) polarography or differential pulse polarography(DPP). The peak potential change per pH unit was -54 mV in the phosphate buffer at $18^{\circ}C$, which indicated that protons were involved in the electrochemical reduction of the 2,3-dioxopiperazine moiety of piperacillin sodium with a $H^{+}e^{-}$ ratio of one. Using a phosphate buffer of pH 4.3, the $1.0{times}10^{-7}$ M piperacillin sodium single peak could be determined by DPP with relative standard deviation of 1.6 %(n=3). Piperacillin sodium could be analyzed with-out interference from penicillin G-potassium, which enabled the employment of DPP as a fast and simple technique for monitoring the synthetic process of the antibiotic.

• Journal of Pharmaceutical Investigation
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• v.18 no.2
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• pp.49-53
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• 1988

Pivaloyloxymethyl ester of piperacillin was synthesized by reacting sodium piperacillin with chloromethyl pivalate, and its chemical structure was determined by infrared and $^1H$ nuclear magnetic resonance spectroscopic methods. The pharmaceutical properties of the ester were investigated to assess its potential as a novel prodrug of piperacillin. The interface transfer of piperacillin and the ester was studied in a two-phase in vitro system composed of aqueous pH buffers and n-octanol. The ester was more lipophilic, and less water soluble above pH 4.0 than piperacillin. Significant antibacterial activity was not observed in the ester in vitro, but the ester was hydrolyzed into the parent drug in the rat liver homogenate. The serum levels of orally administered ester suspension containing 0.1% Tween 80 were measured in rabbits. It was found that the ester showed higher blood level, comparing with no observation of piperacillin in serum, but the time reaching the maximum serum concentration was 5 hr.

• Journal of Pharmaceutical Investigation
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• v.23 no.2
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• pp.71-80
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• 1993

The purpose of this study was to compare the intrinsic absorptivity of piperacillin in the jejunum and the nasal cavity, to investigate the effect of bile salts, fatty acids and their mixed micelles on the intestinal and nasal absorption of piperacilIin, to examine the reversibiIity of bile salt-fatty acid mixed micelles absorption promoting action and to design an effective intranasal drug delivery system for antibiotics. And absorption promoters used were bile salts [sodium cholate (NaC), sodium glycocholate (NaGC)], unsaturated fatty acids [oleic acid (OA), linoleic acid (LA)] and their mixed micelles (NaC-LA). The present study employed the in situ nasal and intestinal perfusion technique in rats. The apparent permeabilities $(P_{app})$ of piperacillin were $0.40{\pm}0.04{\times}10^{-5}cm/sec(mean{\pm}S.E)$ in the jejunum and $1.32{\pm}0.08{\times}10^{-5}\;cm/sec$ in the nasal cavity, which indicated that intrinsic absorptivity of piperacillin was greater in the nasal cavity than in the jejunum. When absorption promoters were used in the rat nasal cavity, the decreasing order of apparent piperacillin permeability $(P_{app},\;10^{-5}\;cm/sec)$, corrected for surface area of absorption, was NaC-LA $(4.62{\pm}0.16)$> NaC $(4.36{\pm}0.32)$>LA$(2.24{\pm}0.26)$ NaGC $(2.17{\pm}0.21)$>OA $(1.53{\pm}0.16)$. The increase in permeability of piperacillin was 3.5-fold in the rat nasal cavity and 1.5-fold in the rat jejunum for formulations containing NaC-LA mixed micelles as compared to those without absorption enhancer. The effect of NaC-LA mixed micellar solutions was synergistic and was greater than that with single adjuvant. The reversibility of nasal mucosal permeability was observed within approximately 2 hr after removal of NaCLA mixed micelles from the nasal cavity. These results suggest that NaC-LA mixed micelles can be used as nasal mucosal absorption promoters of poorly absorbed drugs.

• Journal of Microbiology and Biotechnology
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• v.25 no.8
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• pp.1299-1306
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• 2015

This study aims to investigate the mechanism of action of the cinnamon bark essential oil (CB), when used singly and also in combination with piperacillin, for its antimicrobial and synergistic activity against beta-lactamase TEM-1 plasmid-conferred Escherichia coli J53 R1. Viable count of bacteria for this combination of essential oil and antibiotic showed a complete killing profile at 20 h and further confirmed its synergistic effect by reducing the bacteria cell numbers. Analysis on the stability of treated cultures for cell membrane permeability by CB when tested against sodium dodecyl sulfate revealed that the bacterial cell membrane was disrupted by the essential oil. Scanning electron microscopy observation and bacterial surface charge measurement also revealed that CB causes irreversible membrane damage and reduces the bacterial surface charge. In addition, bioluminescence expression of Escherichia coli [pSB1075] and E. coli [pSB401] by CB showed reduction, indicating the possibility of the presence of quorum sensing (QS) inhibitors. Gas-chromatography and mass spectrometry of the essential oil of Cinnamomum verum showed that trans-cinnamaldehyde (72.81%), benzyl alcohol (12.5%), and eugenol (6.57%) were the major components in the essential oil. From this study, CB has the potential to reverse E. coli J53 R1 resistance to piperacillin through two pathways; modification in the permeability of the outer membrane or bacterial QS inhibition.

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