• Title/Summary/Keyword: cefoperazone

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Pharmaceutical Studies of Cefoperazone Phthalidyl Ester, a Novel Prodrug of Cefoperazone (세포페라존프탈리딜에스텔의 약제학적 연구)

  • Choi, Seung-Ho;Park, Gee-Bae;Choi, Young-Wook;Kim, Johng-Kap
    • Journal of Pharmaceutical Investigation
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    • v.17 no.4
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    • pp.183-188
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    • 1987
  • A new cephalosporin derivative, cefoperazone phthalidyl ester, were synthesized and investigated in terms of dissolution and absorption properties. In comparison with cefoperazone, its phthalidyl ester showed the following characteristics. The mean dissolution time and variance of retention time were more significantly prolonged in simulated intestinal fluid than those in simulated gastric fluid. After a single oral dosing of both cefoperazone and its ester to rabbits, serum concentrations of cefoperazone were measured by bioassay, and the results showed that the ester exhibited much higher and more sustained blood level than the parent drug. The total area under the curve of cefoperazone phthalidyl ester were 10.8 times greater than that of cefoperazone.

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Oral Absorption of Cefoperazone Pivaloyloxymethyl Ester (세포페라존피바로일옥시메칠에스텔의 경구 흡수)

  • Choi, Young-Wook;Park, Gee-Bae;Choi, Seung-Ho;Kim, Johng-Kap
    • Journal of Pharmaceutical Investigation
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    • v.18 no.4
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    • pp.197-201
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    • 1988
  • Pivaloyloxymethyl ester of cefoperazone was synthesized by treating sodium cefoperazone with chloromethyl pivalate and its chemical structure was determined by spectroscopic trials. The pharmaceutical properties of the ester were investigated to assess its potential as a prodrug of cefo perazone. Cefoperazone pivaloyloxymethyl ester was microbiologically inactive itself in vitro, but hydrolyzed into the parent drug in vivo. After a single oral dose of each drug to rabbits, serum concentrations of cefoperazone were determined by high performance liquid chromatographic assay. The ester showed higher and more sustained blood level than cefoperazone. Therefore, the total area under the serum concentration-time curve of the derivative was 16.8 times larger than that of the parent drug.

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Clinical Effectiveness of Cefoperazone(Cefobid) in Obstetrics-Gynecological Infection (부인과감염증(婦人科感染症)에 대(對)한 Cefoperazone(Cefobid)의 임상효과(臨床效果))

  • Park, S.K.;Lim, J.K.
    • The Korean Journal of Pharmacology
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    • v.16 no.2 s.27
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    • pp.71-75
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    • 1980
  • A total of 30 cases of gynecological infection were treated with Cefoperazone at the Department of Ob-Gy, Seoul Baik Hospital, Seoul, Korea from Sept. 1979 to Aug. 1980. Cefoperazone sodium was administered in a dose of 2g/day intramusculary or intravenously for 6 to 13 days. The effective rates of Cefoperazone based on clinical and bacteriological response were 100% in 9 cases of acute non-gonorrheal PID, 5 cases of postpartum endometritis, 2 cases of recurrent non-gonorrheal PID and 80% in acute gonorrheal PID(8 out of 10 cases). A case of recurrent gonorrheal PID and 2 out of 3 cases of postoperative infection responded also satisfactorily to Cefoperazone treatment. There were no drug-related abnormal findings in urinalysis, hematology and blood chemistry. Any particular side effects, except for one case of fever and rash which disappeared spontaneously without any treatment or discontinuation of the drug, were not noted during or after the treatment.

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Oil-Water Interface Transfer of Cefoperazone Pivaloyloxymethyl Ester (세포페라존피바로일옥시메칠에스텔의 유-수 계면 이행에 관한 연구)

  • Choi, Young-Wook;Kim, Johng-Kap
    • Journal of Pharmaceutical Investigation
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    • v.19 no.1
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    • pp.21-27
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    • 1989
  • Kinetic and thermodynamic aspects of the interface transfer of cefoperazone and its pivaloyloxymethyl ester were studied in a two-phase system composed of aqueous buffers and n-octanol by using the absolute reaction rate theory. In terms of the net thermodynamic parameters for the process, ${\Delta}S$ increased and ${\Delta}F$ decreased as the lipophilicity increased. With the increased ratio of forward $(k_f)$ to backward rate constants $(k_b)$, the ester was more lipophilic than cefoperazone, but the aqueous solubility was reduced.

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Pharmacological Studies of Cefoperazone(T-1551) (Cefoperazone(T-1551)의 약리학적 연구)

  • Lim J.K.;Hong S.A.;Park C.W.;Kim M.S.;Suh Y.H.;Shin S.G.;Kim Y.S.;Kim H.W.;Lee J.S.;Chang K.C.;Lee S.K.;Chang K.C.;Kim I.S.
    • The Korean Journal of Pharmacology
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    • v.16 no.2 s.27
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    • pp.55-70
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    • 1980
  • The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.

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Clinical Observation of Cefoperazone in Urinary Tract Infections (요로 감염증에 대한 Cefoperazone(Cefobid)의 임상효과)

  • Yoon Moon-Soo;Cho Dai-Haing;Choi Baik-Nam;Kang Shin-Tai;Bang Jin-Sung;Lim Soo-Kil;Lim Jung-Kyoo
    • The Korean Journal of Pharmacology
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    • v.16 no.2 s.27
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    • pp.77-83
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    • 1980
  • The effectiveness of Cefoperazone in the treatment of urinary tract infection was evaluated in the Department of Urology, St. Mary's hospital from December 1. 1979 to April 30. 1980. In this studies, the cusative organisms were divided into 2 groups; 1) Single form. E. coli (8), Staphylococcus aureus(7), Proteus vulgaris (4), P. morganii(3), S. epidermis (1), Enterococcus(1), Klebsiella (2), N. gonococcus(1). 2) Mixed from: Proteus+E. coli(4), E. coli+other(1), Pseudomonas+Enterococcus(1), Klebsiella+other(1). Effectiveness on urological diseases. 1) Neurogenic bladder: Results were excellent in 3 cases, good in 4 cases and negative effect in 4 cases. 2) Non-gonococcal urethritis: In this group, the therapeutic results were favorable in 88.9% of all cases. (Excellent in 2, Fail in1) 3) Pyelonephritis: All(4 cases) were excellent. 4) Renal stone: Among the 4 cases of renal stone, only one case was responded to cefoperazone. 5) Two cases of urethral stricture, two cases of cystitis, one case of B.P.H. and one case of gonococcal urethritis were all excellent. No serious side effects were observed except slight dizziness in one case.

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Properties of Cephalosporinase Produced by Pseudomonas aeruginosa (Pseudomonas aeruginosa에 의해 생성되는 Cephalosporinase의 특성)

  • 이동준;이호용;최영길
    • Korean Journal of Microbiology
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    • v.24 no.3
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    • pp.302-307
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    • 1986
  • In order to investigate the properties of cephalospornase, a strong antibiotic resistant strain(H 112) was isolated from Pseudomonas aeruginose. The extracted enzyme had the following characteristics. Optimum temperature was 45.deg.C and unstable over $55^{\circ}C$, and optimum pH was 8.5. Cephalosporinase activity was not inhibited by metal ions such as $Mn^{++},\;Cu^{++}\;Fe^{++},\;Fe^{+++}$, and EDTA. But it was inhibited by some antibiotics such as carbenicillin, cefoxitin, cefotaxime, cefamandole, cefoperazone and SDS. The Vmax values of the enzyme were 100 at cephaloridine and 2.8 at cefoperazone, respectively. The molecular weight of cephalosporinase was estimated to be about $37.500{\pm}3,000$ by high performance liquid chromatography and nitrocefin reaction.

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${\beta}-Lactamase$ Inhibitory Activity and Comparative Activity of 6-Benzothiazole Penicillin Derivatives in Combination with ${\beta}-Lactam$ Antibiotics (6-벤조치아졸 페니실린 유도체의 베타락타마제 효소억제력과 베타락탐항생제 병용시 활성비교)

  • Yoon, Sang-Bae;Im, Chae-Uk
    • YAKHAK HOEJI
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    • v.52 no.4
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    • pp.306-310
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    • 2008
  • In vitro ${\beta}-lactamase$ inhibitory activity of 6-benzothiazole penicillins (1, 2, 3 and 4) was compared with clavulanic acid, sulbactam and tazobactam. The inhibitory activity of exomethylene compounds (3 and 4) was stronger than those of non-exomethylene compounds (1 and 2). The sulfide 3 showed stronger inhibitory activity than sulbactam, clavulanic acid andsimilar to tazobactam against ${\beta}-lactamase$ Type I enzymes. The inhibitory activity of 4 was stronger than those of sulbactam, clavulanic acid and tazobactam against Type III and IV enzymes. The in vitro antimicrobial activity of ampicillin or cefoperazone combined with 3 or 4 was stronger than those of ampicillin or cefoperazone alone against many ${\beta}-lactamase$ producing strains to show that compounds 3 and 4 have some synergistic effect. The synergistic activity of 3 and 4 was comparable to sulbactam in some ${\beta}-lactamase$ producing strains, but it was inferior to tazobactam.

Bacteriology and Antibiotic Sensitivity for Diabetic Foot Ulcer (당뇨족 궤양의 세균 역학과 항생제 감수성)

  • Choi, Sang-Rok;Lee, Chang-Kyu;Kim, Deok-Woo;Han, Seung-Kyu;Kim, Woo-Kyung
    • Archives of Plastic Surgery
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    • v.33 no.3
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    • pp.330-334
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    • 2006
  • Polymicrobial nature of diabetic foot infection has been well documented in the literature. Initial antibiotic therapy of diabetic foot infection is usually empiric until reliable culture data is shown. This study was carried out to determine the common bacteriological flora of diabetic foot infection and antimicrobial sensitivity pattern in order to enhance possible empiric treatment. The specimens were obtained from wounds of 207 cases of diabetic foot ulcer, and the bacteriological isolation, and antimicrobial susceptibility tests of the isolates were carried out by standard microbiological methods. Staphylococcus aureus was the most common isolate, with 46.2% of recover rate among total bacterial isolated cases. Among gram-negative organisms, Pseudomonas aeruginosa was most common. Gram-positive organisms showed significant susceptibility to clindamycin, trimethoprim/sulfamethoxazole, and levofloxacin, besides vancomycin. Cefoperazone, piperacillin/tazobactam, and amikacin in addition to imipenem were most effective agents compared to gram-negative organisms. Diabetic foot infection requires use of combined antimicrobial therapy for initial management. Our results indicate that the most effective antibiotic combination for diabetic foot infection of Korean patients is clindamycin plus cefoperazone.

Comparison between Dot Blot Hybridization and Southern Blot Hybridization in Detecting Methicillin Resistant Staphylococcus aureus (Methicillin 내성 Staphylococcus aureus의 검출을 위한 분자유전학적 기법에 관한 연구)

  • 조태흠;김민정;오양효
    • Journal of Life Science
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    • v.9 no.4
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    • pp.358-367
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    • 1999
  • Thirty strains of methicillin resistant Staphylococcus aureus were obtained from the clinical isolates. In order to investigate the pursuit of the pathogens of nosocomial infection, these strains were studied for antibiotic sensitivity as well as its resistant pattern. Among the methods of hybridization which directly confirm the specific antibiotic resistant genes by means of the recently developed specific probe DNA, dot blot hybridization and southern blot hybridization were performed and these two methods were compared in their sensitivity and specificity. Strains that is sensitive to cephalothin to the subject of methicillin resistant Staphylococcus aureus were in 43%. Those that are sensitive to cefoperazone and cefuroxime were 26% and 23%, respectively. In case of MIC, MIC50 of cefoperazone was 8 $\mu\textrm{g}$/$m\ell$, and MIC90 was 128 $\mu\textrm{g}$/$m\ell$ to be the lowest. As the results of plasmid DNA electrophoresis, most of methicillin resistant Staphylococcus aureus strains had more than 4 plasmids. These plasmids digested by BamHI, methicillin resistant Staphylococcus aureus is distributed as 10 fragments with the size of 65 kb to 1.5 kb. Dot blot hybridization were performed to examine the existence of mecA gene to show the detection rate of 50%. Southern blot hybridization were done to see if DNA bands which amplify the activity of digoxigenium-labeled probe by PCR were actually PCR products of mecA gene and it showed the detection rate of 53%. It can be concluded that the southern blot hybridization seemed to be better in sensitivity and specificity when it is compared with the results of dot blot hybridization.

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