• 약학회지
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• 제46권4호
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• pp.290-294
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• 2002

Cephradine is an orally absorbed cephalosporin with a broad spectrum of activity against gram-positive and gram-negative bacteria and is highly resistant to beta-lactamase degradation. The purpose of the present study was to evaluate the bioequivalence of two cephradine capules, Cephradine capsule (Donggu Pharmaceutical Co., reference drug) and Cephradine capsule (Shinpoong Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration. Twenty-six normal volunteers, 24.6 $\pm$ 3.70 years in age and 62.4 $\pm$ 8.99 kg in body weight, were divided into two groups and a randomized 2 $\times$ 2 cross-over study was employed. After one capsule containing 250 mg of cephrdine was orally administered, blood was taken at predetermined time intervals and the concentrations of cephrdine in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as AU $C_{t}$ to $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUCt, $C_{max}$ and $T_{max}$ between two products were 2.89％, 1.05％ and 1.06％, respectively, when calculated against the reference drug. The 90％ confidence intervals were within log0.8 $\leq$ $\delta$ $\leq$ log1.25 (e.g., log0.9803 $\leq$ $\delta$ $\leq$ log1.0734 and log0.9674 $\leq$ $\delta$ $\leq$ log1.220 for AU $C_{t}$, and $C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Cephradine capsules (Shinpoong Pharmaceutical Co.) is bioequivalent to Cephradine capsules (Donggu Pharmaceutical Co.).o.).o.).).o.).

• 한국미생물·생명공학회지
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• 제15권5호
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• pp.361-367
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• 1987

DL-seleno-methionine에 내성을 갖는 변이주, Cephalosporium acremonium MS-92는 무기황과 메치오닌의 Uptake rate가 모균보다 우수하였으며, 세포내에 과량의 메치오닌과 S-adenosylmethionine (SAM)을 축적하였다. 또 C. acremonium에서 무기황의 uptake rate는 시스테인에 의해 크게 저해되었다. Crude enzymes extracts에서 변이주 MS-92 는 cell내에 cysteine을 적게 형성하였다 즉, L.-serine sulfhydrylase 활성이 모균보다 낮았으며 세포내에 시스테인의 양을 간접적으로 알 수 있는 시스테인 분해효소인 cysteine desulfhydrylase 활성치 변이주에는 모균의 약 반이였다. 이상의 결과에서 C. acremonium에서 메치오닌을 만드는 효소들의 조절에는 A. nidulans와 비슷하게 시스테인이 관여한다는 것을 추측할 수 있었다.

• 약학회지
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• 제37권3호
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• pp.295-305
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• 1993

In order to develop oral cephalosporin having a new substituent at 3 position, the synthesis of cephalosporins modified at C-3 and the effect of the substituents on the oral absorption is studied. 7-[(Z)-2-(2-Aminothiazole- 4-yl)-2-methoxyiminoacetamidol-3-[4-(2-pyridyl )piperazinyl] thiocarbonylthiomethyl-3-cephem-4-carboxylic acid (CEN1) and 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyrimid yl)piperazinylthiocarbonylthiomethyl-3-cephem-4-carboxylic acid (CEN2) were synthesized from 4-(2-piridyl)piperazinyl dithiocarbamate potassium salt or 4-(2-pirimidyl)piperazinyl dithiocarbamate potassium salt and cefotaxime. Also pivaloyloxymethyl esters of CEN1 and CEN2, pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl )piperazinyllthiocarbonylthiomethyl-3-cephem-4-carboxylate (CENIP) and pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamidol-3- [4-(2-pyrimid yl)piperazinyllthiocarbonylthiomethyl-3-cephem-4-carboxylate (CEN2P) were synthesized. The in vitro activities of two new oral cephalosporins, CEN1 and CEN2, were compared with the in vitro activities of cefaclor and cefotaxime against a variety of bacterial species. CEN2 has a broad antibacterial spectrum covering Gram-positive and Gram-negative bacteria, similar to that exhibited by CEN1 and cefotaxime. CEN1 and CEN2 were more active in vitro than cefaclor against Streptococcus pyogenes, Klebsiella aerogenes and Enterobacter cloacae.

• Journal of Microbiology and Biotechnology
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• 제11권3호
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• pp.452-457
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• 2001

The glutaryl 7-aminocephalosporanic acid (glutaryl 7-ACA) acylase was purified from Pseudomonas diminuta KAC-1 cells isolated from soil, and characterized. The acylase was purified by procedures including ammonium sulfate fractionation and column chromatographies on DEAE-Sepharose, Phenyl-Sepharose, Q-Sepharose, and Superose 12H/R. The negative acylase was found to be composed of two subunits with molecular masses of approximately 55 kDa and 17 kDa, respectively. The isoelectric point of the enzyme was 4.0. The specific activities of the purified acylase were 8.0 and 7.0 U/mg on glutaryl 7-ACA and glutaryl 7-aminodesacetoxy cephalosporanic acid (glutaryl 7-ADCA), respectively, and $K_m$ values were 0.45 mM for glutaryl 7-ADCA and 0.67 mM for glutaryl 7-ADCA. The enzyme had a pH optimum at 8.0 and a tmperature optimum at $40^{\circ}C$. The acylase catalyzed the synthesis of glutaryl 7-ACA from glutaric acid and 7-ACA as well as the hydrolysis of glutaryl 7-ADCA, although the reaction rate of the synthesis was slower than that of the hydrolysis. In addition, it was found that the enzyme had a glutaryl transferase activity, thereby transferring the glutaryl group from one cephalosporin nucleus to another.

• Biomolecules & Therapeutics
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• 제15권3호
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• pp.182-186
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• 2007

Cefixime is an orally absorbed cephalosporin with a broad spectrum of activity against Gram-negative bacteria and is highly resistant to beta-lactamase degradation. The purpose of the present study was to evaluate the bioequivalence of two cefixime capsules, Suprax capsule (Dong-A Pharmaceutical Co., reference drug) and Alpha-Cefixime capsule (Alpha Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal subjects, $23.5{\pm}3.72$ years in age and $68.3{\pm}8.89$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. There was one week washout period between the doses. After one capsule containing 100 mg of cefixime was orally administered, plasma was taken at predetermined time intervals and the concentrations of cefixime in plasma were determined using HPLC with UV detector. The pharmacokinetic parameters such as $AUC_{t}$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_{t}$, $C_{max}$ and $T_{max}$ between two products were -3.91%, -2.23% and -3.18%, respectively, when calculated against the reference drug. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of $log0.8{\leq}{\delta}{\leq}log1.25$ (e.g., $log0.8786{\leq}{\delta}{\leq}log1.0523$ and $log0.8889{\leq}{\delta}{\leq}log1.0512$ for $AUC_{t}$ and $C_{max}$, respectively). The 90% confidence intervals using untransformed data was within ${\pm}20%$(e.g., $-10.37%{\leq}{\delta}{\leq}6.73%$ for $T_{max}$). All parameters met the criteria of KFDA for bioequivalence, indicating that Alpha-Cefixime capsule (Alpha Pharmaceutical Co.) is bioequivalent to Suprax capsule (Dong-A Pharmaceutical Co.).

• 한국임상약학회지
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• 제8권1호
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• pp.19-22
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• 1998

Cefixime is an orally absorbed 3rd generation cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and is highly resistant to $\beta-lactamase$ degradation. This study was carried out to evaluate the bioavailability of a new test drug of cefixime (100 mg/capsule) relative to the reference drug. The bioavailability was conducted on 20 healthy volunteers who received a single dose (400 mg) of the test and the reference drugs in the fasting state, in a randomized balanced 2-way crossover design. After dosing, serial blood samples were collected for a period of 12 hours. Plasma was analyzed for cefixime by a sensitive and validated HPLC assay. The major pharmacokinetic parameters $(AUC_{0-12hr},\;C_{max},\;T_{max})$ were calculated from the plasma concentration-time data of each volunteer. The $AUC_{0-12hr},\;C_{max}\;and\;T_{max}$ of the test drug were $36.91\pm11.85\;{\mu}g{\cdot}hr/ml,\;5.47\pm1.61\;{\mu}g/ml,\;and\;4.00\pm0.65\;hr,$ respectively, and those of the reference drug were $34.08\pm8.81\;{\mu}g{\cdot}hr/ml,\;5.25\pm1.40\;{\mu}g/ml,\;and\;4.20\pm0.62\;hr$, respectively. Mean differences of those parameters were 8.32, 4.29, and $4.76\%$, respectively, and the least significant differences at $\alpha$=0.05 for $AUC_{0-12hr},\;C_{max},\;T_{max}$ were 16.02, 13.78, and $11.76\%$, respectively. In conclusion, the test drug was bioequivalent with the reference drug.

• 한국임상수의학회지
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• 제29권3호
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• pp.233-236
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• 2012

Cefquinome은 제4세대 cephalosporin으로 동물전용의약품으로 개발되었으며, ${\beta}$-lactamases에 대해서 매우 안정하고, 그람 음성 세균 및 양성 세균에 대한 광범위한 살균력을 가지고 있다. 본 연구는 현재 시판중인 cefquinome 주사제를 이유 자돈에 2 mg/kg 용량으로 근육 주사한 후 약물동태학적 특성을 파악하여 두 제제의 생물학적 동등성을 평가하였다. Cefquinome의 혈중 농도는 액체크로마토그래프/질량분석기를 이용하여 분석하였으며, 생물학적 동등성을 판정하기 위한 약물동태학적 인자로는 혈중 최고 농도 ($C_{max}$)와 혈장 농도 곡선하 면적 ($AUC_{0{\rightarrow}{\infty}}$)을 사용하였다. 시험약과 대조약의 혈중 최고 농도는 $4.34{\pm}0.58{\mu}g/mL$과 $4.22{\pm}0.47{\mu}g/mL$로 각각 나타났으며, 혈장 농도 곡선 하 면적은 $10.43{\pm}1.96{\mu}g{\cdot}h/mL$과 $10.25{\pm}2.98{\mu}g{\cdot}h/mL$로 관찰되었다. 로그변환한 약물동태학적 인자의 평균비율의 90% 신뢰 구간은 $C_{max}$의 경우 0.941-1.115이었고, $AUC_{0{\rightarrow}{\infty}}$의 경우 0.927-1.172로서 생물학적 동등성 기준인 0.8-1.25를 모두 만족시켰다. 이상의 결과로 시판중인 두 cefquinome 제제는 생물학적으로 동등하다고 판단된다.

• 한국임상약학회지
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• 제7권1호
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• pp.17-21
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• 1997

Cefaclor is a second generation cephalosporin antibiotic that shows a potent antibacterial activity against both Gram-positive and Gram-negative bacteria, when it is orally administered. Due to its patent expiration, a number of generic drugs have been marketed, but not yet elucidated to ensure therapeutic equivalence. In this study, cefaclor capsules manufactured by Chong Kun Dang were bioequivallently assessed by comparing with $Ceclor^{TM}$ introduced originally by Daewoong Lilly. A total of 16 healthy male volunteers were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of cefaclor in plasma were measured upto 6 hours following a single oral administration of two capsules (500 mg of cefaclor) by high-performance liquid chromatography with UV detection. Although the plasma concentration at 6 hours was not detected, the computed half-life of cefaclor was approximately 0.5 hours. The area under the concentration-vs-time curve from 0 to 4 hours $(AUC_{0-4h})$ was calculated by the trapezoidal summation method. The differences in mean values of $AUC_{0-4h}$, peak plasma concentration $(C_{max})$, and time to peak concentration $(T_{max})$ between the two products were $4.63\%,\;1.84\%,\;and\3.28\%$, respectively. The least significant differences at $\alpha4= 0.05 for $AUC_{0-4h},\;C_{max},\;and\;T_{max}\;were\;6,53\%,\;4.05\%,\;and\;6.47\%$, respectively. In conclusion, the test drug was bioequivalent with the reference drug.

• 약학회지
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• 제27권3호
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• pp.185-205
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• 1983

Penicillins and cephalosporins are biosynthesized from L-.alpha.-aminoadipic acid, L-cysteine and L-valine. A tripeptide, LLD-$\delta$-($\alpha$-aminoadipyl)cysteinylvaline(LLD-ACV) was isolated from fermentation broths of Cephalosporium acremonium as well as of Penicillium chrysogenum and it was proved that the LL-$\delta$-($\alpha$-aminoadipyl cysteine was formed first in mycelia, to which valine would be connected to give LLD-ACV. However, several points are still unsolved; first, what mechanism is involved in the configurational change from L-valine to D-valine, second, what kind of cyclization mechanism gives a $\betha$-lactam ring and a thiazolidine ring and third, what is the pathways for the ring expansion from penicillins to cephalosporins. At present, it seems clear that LLD-ACV is cyclized to give isopenicillin N, which is transformed to penicillin N and further to cepbalosporin C. Other hydrophobic penicillins, including benzyl penicillin and penicillin V, are formed from isopenicillin N by acyl-exchange reactions catalyzed by penicillin transferase, rather than by acylation reaction on 6-aminopenicillanic acid(6-APA), which was isolated from the fermentation broth of P. chrysogenum and which would be formed by hydrolysis of $\delta-(\alpha$-amincadipyl)amido moiety at the C-6 position in isopenicillin N or penicillin N by penicillin acylase. Acylation of 6-APA is catalyzed also by penicillin acylase, but the reaction is proved not to be involved in penicillin biosynthesis. Understanding the biosynthesis of penicillins and cephalsoporins would provide solutions to increase in fermentation yields of penicillins, especially of cephalosporins and a solution to biological production of 7-aminocepbalosporanic acid (7-ACA) which is of importance in pharmaceutical industry. Still regulation mechanisms in penicillin and cephalosporin biosynthesis are unveiled at all.

• 한국임상약학회지
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• 제20권1호
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• pp.78-84
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• 2010

Background: Clostridium difficile is the primary reason of the nosocomial diarrhea. The antimicrobial therapy plays a central role in the pathogenesis of Clostridium difficile associated diarrhea (CDAD). Although nearly all classes of antimicrobial agents have been associated with CDAD, clindamycin and the third-generation cephalosporins have traditionally been considered to the greatest risk factor. Recent studies have also implicated fluoroquinolones as high-risk agents due to increasing use of the agents. This study was to determine the incidence and the risk factors of CDAD related to the administered antibiotics and to assess the therapeutic regimen of metronidazole or vancomycin based on the C. difficile toxin assay Methods: A retrospective study was performed in patients with Clostridium difficile toxin assay at I Hospital (Incheon, South Korea) during the period from January 2007 through December 2007. Administrative, laboratory, and pharmacy data were collected from Electronic Medical Databases. Results: The analysis included 129 reported C.difficile toxin assay results, with 42 positive cases and 87 negative cases. Significant antibiotic risk factors for CDAD included the use of the fourth-generation cephalosporinse (OR=5.97, 95% CI 1.37-25.98, P=0.017). Administration of metronidazole was protective against CDAD (OR=0.30, 95% CI 0.12-0.74, P=0.009). Prolonged antimicrobial therapy has been associated with an increased risk of CDAD. The third-generation cephalosporins (OR=3.81, 95% CI 1.08-13.41, P=0.037) and aminoglycoside (OR=5.50, 95% CI 1.43-21.10, P=0.013) demonstrated greater risk for CDAD over 15 days than 8days or less days of treatment duration. Conclusions: The fourth and third generation cephalosporin, aminglycoside were the significant risk factors compared with other antibiotics, whereas metronidazole appears to be protective. The longer duration of antiobiotic use increased CDAD.