• Journal of Pharmaceutical Investigation
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• 제18권3호
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• pp.139-144
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• 1988

Piperacillin phthalidyl ester was synthesized by reacting piperacillin with triethylamine and bromophthalide in acetone and its chemical structure was determined by UV, IR, and PMR. The partition coefficient of the ester was increased and the ester was more lipophilic and less water soluble than piperacillin. The ester did not show the antimicrobial activity against Bacillus subtilis ATCC 6633 in vitro, but when hydrolyzed, the parent drug of ester, piperacillin, revealed antimicrobial activity in vivo. After a single oral dose of both piperacillin and the ester to rabbits, the serum piperacillin concentration was measured by bioassay. The ester exhibited improved pharmatokinetic characteristics: $T_{max}\;of\;2hr,\;C_{max}\;of\;4.26{\mu}g{\cdot}ml^{-1},K_{el}\;of\;0.057hr^{-1},\;and\;total\;AUC\;of\;85.42{\mu}g{\cdot}hr{\cdot}ml^{-1}$. Piperacillin on the other hand, did not exhibit any gastro-intestinal absorption.

• Journal of Pharmaceutical Investigation
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• 제18권2호
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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.

• Archives of Pharmacal Research
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• 제23권3호
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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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• 제15권4호
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• pp.186-197
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• 1985

Polymorphs of piperacillin monohydrate were prepared by various sedimentation methods from piperacillin base for the purpose of developing piperacillin preparations for oral use. Solubility and dissolution rate of each form of the polymorphs were compared with each other. It was found that Form IV showed the highest solubility and the fastest dissolution rate among four forms of polymorphs. In general, the solubility and dissolution rate of two amorphous forms, Form IV and II were higher than those of two crystal forms, Form I and III. The apparent dissolution rates in the artificial gastric juice within 60 minutes were $0.65{\times}10^{-6}mole{\cdot}min^{-1}\;cm^{-2}$ for From IV, $0.36{\times}10^{-6}mole{\cdot}min^{-1}{\cdot}cm^{-2}$ for From II, $0.30{\times}10^{-6}mole{\cdot}min^{-1}{\cdot}cm^{-2}$ for From III and $0.18{\times}10^{-6}mole{\cdot}min^{-1}{\cdot}cm^{-2}$ for From I, respectively.

• Journal of Pharmaceutical Investigation
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• 제23권2호
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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.

• 한국임상약학회지
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• 제27권2호
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• pp.83-91
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• 2017

Background: Piperacillin/tazobactam (TZP) is an antibiotic against a broad spectrum of gram-positive, gram-negative, and aerobic and anaerobic strains of bacteria. Due to changes in its pharmacokinetic and pharmacodynamic parameters by TZP-treated patients' renal functions and obesity, it is important to administrate and monitor TZP based on their renal functions and Body Mass Index (BMI) levels. The purpose of this study was to determine the appropriateness of administration doses of TZP based on renal functions of obese cancer patients in a tertiary hospital. Methods: This study was retrospectively conducted with obese cancer patients with $BMI{\geq}30kg/m^2$ in a tertiary hospital, Korea from September 2004 to August 2014. Data were collected through Electronic Medical Record (EMR) which contained laboratory data and TZP dosing of each patient. Results: Among 7,058 patients during the study period, 102 prescriptions were selected based on inclusion and exclusion criteria and classified by their renal functions. Although TZP should be used based on patients' renal functions to adjust its dose, its initial dose and dosing interval were consistently used without considering patients' renal functions on a regular basis. Especially, in the comparison with FDA dosing standard of TZP, approximately twice patients with $20mL/min{\leq}CrCl{\leq}40mL/min$ received domestically 4.5 g instead of 2.25 g as the TZP starting dose. Conclusion: The appropriate doses of TZP were administered to almost all of obese cancer patients; however, the recommended TZP dose was different between Korea and other countries by twice the amount. Further related studies are necessary to clearly determine the results, to optimize TZP treatment for obese patients with cancer in clinical practice, and to design and develop new TZP formulations for them in pharmaceutical industry.

• Archives of Pharmacal Research
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• 제18권6호
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• pp.423-426
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• 1995

SM-101 is a mixture of metampicillin and sulbactam(2:1). The antibacterial activities of SM-101 were compared with those of metampicillin, piperacillin and Augmentin. It showed powerful antibacterial activities against major strains. Except P. anruginosa and S. marcescens, the in vitro antibacterial activity of SM-101 was higher than those of metampicillin, piperacillin and Augmentin against Staphylococcus spp., Streptococcus spp., Moganella morganii, E. Coil, and Proteus spp. The $ED_{50}$ values of SM-101 were two-fold or greater than those of metampicillin, piperacillin and Augmentin against $\beta-lactamase$ producing strains, p. mirabilis GN79 and M. morganiii MB4-11. The in vivo efficacy of SM-101 was more active than metampicillin and pipeeracillin and similar to Augmentin against S. aureus Smith, E coli MB4-01 and K. pneumoniae MB4-02.

• 대한임상검사과학회지
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• 제40권2호
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• pp.75-79
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• 2008

86 clinical isolates of Acinetobacter baumannii and 116 clinical isolates of Pseudomonas aeruginosa strains isolated from clinical specimens were collected from a hospital in Daegu city area. We investigated the Antimicrobial susceptibility patterns of A. baumannii and P. aeruginosa isolated from sputum, urine, wound, blood, nasal swab, body fluid. The antimicrobial resistance of A. baumannii were shown 96% for piperacillin, carbenicillin 82%. cefotaxime 78%, ciprofloxacin 77%, sulfamethoxazole/trimethoprime 76%, ceftazidime 75%, tobramycin 72%. For P. aeruginosa, the resistance of cefotaxime and sulfamethoxazole/trimethoprime were 100%, carbenicillin 49%, piperacillin 47%, ticarcillin 45%, ticarcillin/ clavulanic acid 40%.

• 대한임상검사과학회지
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• 제39권3호
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• pp.178-182
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• 2007

During 2006, the antibiotic resistance rate were investigated in gram negative bacteria. Resistance to piperacillin were detected at 60% in Escherichia coli, and 37% in Klebsiella pneumoniae. Ceftriaxone were detected 58% in Enterobacter cloacae, 52% in Acinetobacter baumannii, 43% in Enterobacter aerogenes and 76% were detected in Serratia marcescens. Between 1998 and 2007 antibiotic resistance rate were decreased in seven types antibiotic drugs. but, ceftazidime were increased from 12 to 20% during this times. In addition, E. coli, E. cloacae, A. baumannii and E. aerogenes were more isolated from May to June and K. pneumoniae and S. marcescens were more isolated from July to September. We should monitor and control antibiotic use and regularly survey antibiotic resistance patterns among pathogens in the hospital.

• 약학회지
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• 제40권3호
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• pp.343-346
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• 1996

The influence of LB20304a, a new fluoroquinolone antibiotic agent, on microflora of caecum in mice was compared with those of ciprofloxacin and piperacillin after administration of drugs for 5 days. Selective medium (CCFMA) was used for the isolation of Clostridium difficile from the specimens of mouse caecum. The emergence of C. difficile in mouse caecum induced by LB20304a was lower than that by ciprofloxacin or piperacillin at day 1 and day 7 after completing administration of drugs.