• 한국임상약학회지
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• 제22권3호
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• pp.234-238
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• 2012

Background: Valproic acid is widely used in the treatment of generalized tonic-clonic and partial seizures. The carbapenem class is the most potent and widest spectrum of antimicrobial activity. Concomitant administration of carbapenems and valproic acid has been reported to decrease the serum concentration of valproic acid, which is sometimes associated with seizures. The purpose of this study is to evaluate the changes in valproic acid concentration and half life and the frequency of seizure during concomitant administration of valproic acid and carbapenems. Method: This study was performed retrospectively on total 40 cases with identified valproic acid concentration during concomitant administration of valproic acid and carbapenems at Kangbuk Samsung Hospital from February 1st, 2006 to October 31st, 2011. Patients were classified into 3 groups: ertapenem group (n=14), imipenem group (n=12), meropenem group (n=14). Results: The mean serum concentrations in each group during combined treatment were $9.50{\pm}8.84$, $21.88{\pm}8.17$ and $10.62{\pm}8.67$ mg/L, respectively (p < 0.001). The mean half-lives in each group during concurrent use of valproic acid and carbapenems were $3.18{\pm}0.81$, $4.63{\pm}1.97$ and $2.67{\pm}1.69$ hr, respectively (p < 0.001). The valproic acid serum concentration decreased by 75.5%, 54.1% and 84.1% and the half-life of valporoic acid decreased by 65.6%, 35.7% and 73.5%, respectively. Total cases with seizure were 12(30%) with 5(35.7%) in the ertapenem group, 3 (25.0%) in the imipenem group and 4(28.6%) in the meropenem group (p=0.911). There were no specific factors to influence on seizure development during combined treatment. Conclusion: Concurrent use of carbapenems and valproic acid should be avoided. If concomitant administration is essential, very close serum concentration monitoring and clinical observation are necessary.

• Bulletin of the Korean Chemical Society
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• 제22권6호
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• pp.553-558
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• 2001

A stereoselective synthesis of $1\beta-aminocarbapenems$ (11a-c) starting from-4-acetoxy-2-axetidinone derivative 4 is described. 4-Acetoxy-2-azetidinone derivative (4) was reacted with lithium enolate of benzophenone limine of glycine phenyl ester (5f) to give alkylated product (R)-6f in good yield with high diastereoselectivity. The alkylated procudt (R)-6f was transformed to thioesters (7a-c) by transesterification with thiols, Thioesters (7a-c) were converted to their oxalimides (8a-c), followed by the phosphite-mediated reductive cyclization to give carbapenems (9a-c). Removal of all protecting groups of carbapenems (9a-c) afforded $1\beta-aminocarbapenems$ (11a-c).

• Bulletin of the Korean Chemical Society
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• 제7권5호
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• pp.405-407
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• 1986

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.179.3-180
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• 2002

• Bulletin of the Korean Chemical Society
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• 제8권2호
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• pp.130-132
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• 1987

• Bulletin of the Korean Chemical Society
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• 제7권4호
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• pp.325-327
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• 1986

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.34-35
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• 1993

The Development of new asymmetric induction methods useful for syntheses of biologically active natural products and drugs, using C4-chiral 1,3-th-iazolidine-2-thiones, has been a recent focus of interest. 1-8) The present account describes the significance of particular heterocycles in the synthetic development of new 1${\beta}$-substituted carbapenems. A fungal metabolite, (＋)-thienamycin (1) has attracted one's attention as a hopeful candidate for new-generation antibiotic drugs because of its strong antimicrobial activities and wide antimicrobial spectra due to the extensive inhibition against various ${\beta}$-lactamases. However, it has been serious problems toward a practically useful drug that (＋)-thienamycin is fairly labile in the solution and can be metabolized by renal dehydropept- idase-I (DHP-I). Recently, a Merck Sharp ＆ Dohme research group exploited a non-natural ${\beta}$-lactam, imipenem (2) which has been appeared in the drug market as the first carbapenem-type antibiotic drug. 9) However 2 must be used with a DHP-I inhibitor, cilastatin sodium (3).9) Thus, a 1,${\beta}$-methyl- carbapenem derivative 4 has been disclosed by the same group. 10) It seems to be more hopeful candidate as a new-generation antibiotic because it can directly resist against metabolism by the renal DHP-1 without an enzyme inhibitor 3. 10)

• The Korean Journal of Medicine
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• 제99권3호
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• pp.149-157
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• 2024

목적: 장내세균에서 3세대 cephalosporin 계열 항생제에 내성을 나타내는 주된 내성 기전은 extended spectrum β-lactamase(ESBL)를 생성하는 것이다. ESBL 생성 장내세균은 ESBL 생성균이라고 하더라도 piperacillin/tazobactam 감수성 균인 경우 piperacillin/tazobactam을 사용해 볼 수 있으며 후향적 연구에서 carbapenem 계열 항생제를 투여한 경우에 비해 열등하지 않은 치료 효과가 보고된 바 있다. 하지만 미국감염학회 2023년 지침에서는 ESBL 생성 그람음성균 감염에서 carbapenem 계열 항생제를 권고하고 piperacillin/tazobactam 감수성인 그람음성균이더라도 carbapenem 계열 항생제를 투여하도록 하고 있다. 하지만 carbapenem 내성 장내세균의 증가 등으로 비 carbapenem 계열의 항생제들의 사용 필요성에 대한 평가는 아직도 필요한 상황이다. 이에 제주대학교병원의 ESBL 생성 장내세균속 균혈증 환자들의 carbapenem과 비 carbapenem 계열 항생제의 치료 효과를 보고한다. 방법: 2021년 1월부터 12월까지 527명의 성인 장내세균속 균혈증 환자들 중에서 ESBL 생성 장내세균속 환자 152명을 대상으로 후향적 자료를 수집하고 3개월 이내 장내세균 감염이 있었던 환자들과 30일 후 추적 관찰을 하지 못한 환자들을 제외하고 분석하였다. 결과: 총 118명의 ESBL 생성 장내세균속 균혈증 환자들중에서 54명의 환자가 확정적 항생제로 비 carbapenem 계열 항생제로 치료하였고 64명의 환자가 carbapenem 계열 항생제로 치료하였다. Kaplan-Meier 생존 분석 방법으로 30일 치료 실패율과 사망률을 분석한 결과 30일 치료 실패율은 비 carbapenem군이 16.7%, carbapenem군이 18.8%로 양 군 간의 유의한 차이는 없었다(p = 0.65). 30일 사망률은 비 carbapenem 계열군이 14.8%, carbapenem 계열군이 17.2%로 양 군 간의 유의한 차이는 없었다(p = 0.63). 전체 환자들 중에서 치료 실패한 환자들을 다변량 로지스틱 회귀 분석한 결과에서 요로 감염 외 감염과 이전 30일 이내 항생제 사용력이 있는 경우 치료 실패의 위험인자로 확인되었다. 결론: ESBL 생성 장내세균속 균혈증 환자들은 국내에서 확정적 항생제로 비 carbapenem 계열의 항생제를 사용해 볼수 있으나 중증 환자들을 포함한 다기관, 전향적 후속 연구들이 필요하다.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
• /
• pp.167.3-168
• /
• 2000

• 대한화학회지
• /
• 제30권1호
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• pp.138-142
• /
• 1986