预约演示
更新于：2025-10-18
Doripenem
多利培南
更新于：2025-10-18
概要
基本信息
最高研发阶段批准上市 |
最高研发阶段(中国)临床3期 |
特殊审评孤儿药 (美国) |
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结构/序列
分子式C15H26N4O7S2 |
InChIKeyNTUBEBXBDGKBTJ-WGLOMNHJSA-N |
CAS号364622-82-2 |
关联
50
项与 多利培南 相关的临床试验CTR20180182
健康受试者中注射用多立培南单剂药代动力学及药代动力学/药效学研究
CTR20170854
评价注射用多立培南治疗复杂性尿路感染患者有效性和安全性的随机、盲法、阳性药平行对照、多中心临床研究
CTR20130289
随机、盲法、注射用美罗培南平行对照、多中心试验评价注射用多立培南治疗复杂性尿路感染的安全性和有效性
100 项与 多利培南 相关的临床结果
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100 项与 多利培南 相关的专利（医药）
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1,471
项与 多利培南 相关的文献（医药）2025-10-03JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Phenotypic and genotypic profiles of clinical isolates of various Nocardia species to carbapenems and fluoroquinolones
Article
作者: Xue, Jiaoyu ; Jiang, Tingfei ; Zhang, Mingrui ; Shi, Dongyan ; Yang, Jing
Abstract:
Objectives:
To establish patterns of the antimicrobial susceptibility of Nocardia species to carbapenems and fluoroquinolones and analysis of phenotypic–genotypic correlations.
Methods:
Isolates were identified to the species using 16S rRNA, secA1, or rpoB gene sequencing analysis. The antimicrobial susceptibility testing was performed using the broth microdilution method, and WGS was employed to analyse the presence of resistance genes and/or mutations of Nocardia species against carbapenems and fluoroquinolones.
Results:
Among 143 Nocardia isolates, N. farcinica (27.27%, 39/143) and N. cyriacigeorgica (25.17%, 36/143) were the most common species, followed by N. abscessus Complex (18.88%, 27/143). The MIC90s of the seven carbapenems were 8 mg/L for doripenem, 8 mg/L for meropenem, 16 mg/L for ertapenem, 16 mg/L for biapenem, 64 mg/L for imipenem, 64 mg/L for faropenem and 128 mg/L for tebipenem, respectively. The susceptibility rates to imipenem were 76.9% and 88.9% for N. farcinica and N. cyriacigeorgica, respectively, but only 14.3% and 0% for N. otitidiscavarium and N. brasiliensis, respectively. Further, 90% of N. brasiliensis and 50% of N. otitidiscaviarum isolates were susceptible and intermediate to meropenem. WGS identified blaFAR-1 gene in N. farcinica and blaAST-1 gene in N. cyriacigeorgica, respectively. The MIC90s of the four fluoroquinolones were 1 mg/L for sitafloxacin, 4 mg/L for nemonoxacin, 4 mg/L for moxifloxacin and 16 mg/L for ciprofloxacin, respectively. The susceptibility rate of Nocardia species to ciprofloxacin was low except for N. farcinica. The resistance to fluoroquinolones arise from mutations in the gyrA gene.
Conclusions:
Nocardia spp. exhibited varying patterns of susceptibility to carbapenems and fluoroquinolones respectively. Importantly, different Nocardia spp. exhibited different patterns of susceptibility to carbapenems and fluoroquinolones, respectively.
2025-10-01YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
Clinical Pharmacological Research Aiming to Optimize Therapeutic Strategies in Specific Populations
Review
作者: Tanaka, Ryota
In the field of drug development, pharmacokinetic studies primarily focus on adult and pediatric populations, resulting in limited pharmacokinetic data for specific populations such as neonates, pregnant women, and critically ill patients. Optimizing drug therapy for these populations requires dosing strategies that are personalized for individual patients, and are based on pharmacokinetic/pharmacodynamic analyses and therapeutic drug monitoring. In our study of patients admitted to intensive care unit (ICU), the pharmacokinetic parameters of doripenem differed from those in non-ICU patients, with higher pharmacokinetic/pharmacodynamic breakpoints in ICU patients. Population pharmacokinetic modeling of doripenem revealed that prolonged infusion for 4 h was necessary for critically ill patients undergoing continuous renal replacement therapy. In patients with hematological malignancies, inflammatory markers such as C-reactive protein (CRP) significantly affected the intra-individual pharmacokinetic variability of voriconazole, highlighting the need for dose titration according to CRP levels. Furthermore, febrile neutropenia (FN) significantly increased vancomycin clearance in children, requiring higher daily doses than in children without FN. In contrast, augmented renal clearance, but not FN, significantly affected teicoplanin clearance in adults. Physiologically based pharmacokinetic modeling of sublingual buprenorphine facilitated prediction of drug exposure in pregnant women and their fetuses. Post hoc optimization of sublingual absorption using concentrations observed in the mothers markedly improved prediction of fetal exposure. These findings underscore the importance of personalized pharmacokinetic assessments to improve individualized therapeutic strategies in specific populations, and to aim for optimizing efficacy while minimizing adverse effects. Future research integrating mathematical modeling and simulation techniques is expected to improve dosing precision.
2025-08-05Microbiology Spectrum
Specific variants in
ftsI
reduce carbapenem susceptibility in
Pseudomonas aeruginosa
Article
作者: Sato, Yukari ; Nakata, Noboru ; Yano, Hirokazu ; Yahara, Koji ; Sugai, Motoyuki
ABSTRACT:
The
ftsI
locus of gram-negative bacteria encodes penicillin-binding protein 3 (PBP3), a common target of β-lactam antibiotics. Recent genomic surveillance of carbapenem-resistant
Pseudomonas aeruginosa
revealed that 17% of strains possessed nonsynonymous substitution in
ftsI
. However, the contribution of
ftsI
nonsynonymous substitution alone to the antimicrobial susceptibility of
P. aeruginosa
has not been formally evaluated. Therefore, we assessed the effect of
ftsI
nonsynonymous substitutions alone on β-lactam susceptibility in recombinant
P. aeruginosa
strains. The nonsynonymous substitutions C265G (Leu89Val), C1379T (Met460Thr), T1412G (Val471Gly), C1510T (Arg504Cys), C1579A (Pro527Thr), C1579T (Pro527Ser), C1599A (Phe533Leu), and G1609C (Val537Leu) were introduced into
ftsI
in an antimicrobial-susceptible strain via homologous recombination. Then, their β-lactam susceptibilities were investigated using the broth microdilution method and growth parameter analysis for the growth curves. The introduction of the N-terminal Leu89Val mutation did not alter β-lactam susceptibility. By contrast, the introduction of penicillin-binding (PB) domain mutations (Met460Thr, Val471Gly, Arg504Cys, Pro527Thr, Pro527Ser, Phe533Leu, or Val537Leu) reduced the susceptibility to meropenem and doripenem by two- to eightfold in MIC. Arg504Cys, the most common mutation encountered clinically, reduced susceptibility to cefepime by fourfold. Growth parameter analysis revealed that, conversely, these PB domain mutations generally increase the susceptibility to cefiderocol and piperacillin. The cocrystal structures of PBP3 with β-lactams suggest that the positions of PB domain mutations can affect the mobility of previously proposed key residues, namely, Tyr409, Arg489, Tyr503, Tyr532, Phe533, and the KSGT motif, via intramolecular interactions. These data demonstrated that seven specific variants in
ftsI
are genetic signals of bacterial adaptation to carbapenems.
IMPORTANCE:
Previous studies have reported the occurrence of
ftsI
mutations under various genetic backgrounds in
Pseudomonas aeruginosa
clinical isolates. However, the nature of
ftsI
mutations by themselves has not been thoroughly investigated under a common genetic background using recombinant strains. This study presents experimental data on the effect of
ftsI
point mutations alone on bacterial susceptibility to a wide range of antipseudomonal β-lactams. This study found that seven specific penicillin-binding domain mutations in FtsI/PBP3 reduced the efficacy of carbapenems but increased the efficacies of piperacillin and cefiderocol. This key finding will facilitate the development of therapeutic options for carbapenem-resistant
P. aeruginosa
-associated infections. Furthermore, this study contributes to the development of a reliable database collating resistance-associated point mutations, which would aid the interpretation of genomic data on
P. aeruginosa
clinical isolates.
100 项与 多利培南 相关的药物交易
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研发状态
批准上市
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 脑膜炎球菌感染 | 日本 | 2015-03-17 | |
| 小儿感染 | 日本 | 2013-04-10 | |
| 医院获得性肺炎 | 欧盟 | 2008-07-25 | |
| 医院获得性肺炎 | 冰岛 | 2008-07-25 | |
| 医院获得性肺炎 | 列支敦士登 | 2008-07-25 | |
| 医院获得性肺炎 | 挪威 | 2008-07-25 | |
| 呼吸机相关性肺炎 | 欧盟 | 2008-07-25 | |
| 呼吸机相关性肺炎 | 冰岛 | 2008-07-25 | |
| 呼吸机相关性肺炎 | 列支敦士登 | 2008-07-25 | |
| 呼吸机相关性肺炎 | 挪威 | 2008-07-25 | |
| 复杂腹腔感染 | 美国 | 2007-10-12 | |
| 复杂的尿路感染 | 美国 | 2007-10-12 | |
| 肾盂肾炎 | 美国 | 2007-10-12 | |
| 革兰氏阴性菌感染 | 日本 | 2005-09-08 | |
| 革兰氏阳性细菌感染 | 日本 | 2005-09-03 | |
| 泌尿道感染 | 日本 | 2005-08-30 | |
| 细菌感染 | 日本 | 2005-07-25 | |
| 呼吸道感染 | 日本 | 2005-07-25 |
未上市
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 急腹症 | 临床3期 | 美国 | 2010-12-01 | |
| 急腹症 | 临床3期 | 阿根廷 | 2010-12-01 | |
| 急腹症 | 临床3期 | 巴西 | 2010-12-01 | |
| 急腹症 | 临床3期 | 智利 | 2010-12-01 | |
| 急腹症 | 临床3期 | 哥伦比亚 | 2010-12-01 | |
| 急腹症 | 临床3期 | 拉脱维亚 | 2010-12-01 | |
| 急腹症 | 临床3期 | 立陶宛 | 2010-12-01 | |
| 急腹症 | 临床3期 | 巴拿马 | 2010-12-01 | |
| 腹腔脓肿 | 临床3期 | 美国 | 2010-12-01 | |
| 腹腔脓肿 | 临床3期 | 阿根廷 | 2010-12-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床3期 | - | 13 | Doripenem 1 g q8h | 願範鏇願鹽襯鹹憲艱艱(積鹹廠艱網鹽積鏇齋築) = 遞築餘鑰鏇選積鹽醖憲 獵簾鬱廠壓選網積鏇艱 (積膚願壓鑰簾膚淵簾繭 ) 更多 | - | 2015-12-28 | |
临床1期 | 52 | (Neonates (<4 weeks in chronological age)) | 齋鹽窪憲憲廠齋壓獵鬱(鹹餘選壓選製鏇範膚鏇) = 膚簾蓋夢淵鹹蓋齋艱壓 網憲襯齋構製範夢範膚 (鹹積顧構餘鹽鏇獵廠窪 ) 更多 | 积极 | 2015-08-01 | ||
(infants >4 weeks.) | 齋鹽窪憲憲廠齋壓獵鬱(鹹餘選壓選製鏇範膚鏇) = 齋鏇醖廠製觸遞鑰獵憲 網憲襯齋構製範夢範膚 (鹹積顧構餘鹽鏇獵廠窪 ) 更多 | ||||||
N/A | 粒细胞减少性发热 一线 | - | 範膚壓網餘製築窪憲憲(鹹窪範壓繭構衊遞積鬱) = 遞淵遞醖遞製廠遞膚壓 簾蓋網齋築鹹製簾艱築 (憲膚醖築糧觸憲遞鏇繭 ) 更多 | 积极 | 2015-05-21 | ||
範膚壓網餘製築窪憲憲(鹹窪範壓繭構衊遞積鬱) = 憲選鹹顧選餘廠廠膚醖 簾蓋網齋築鹹製簾艱築 (憲膚醖築糧觸憲遞鏇繭 ) 更多 | |||||||
临床3期 | 41 | (Doripenem) | 築襯鑰鬱鹽憲觸遞築築 = 鏇膚獵蓋願壓憲構顧廠 蓋選遞鏇繭壓獵遞製顧 (齋衊鹽蓋糧衊願糧繭艱, 選廠積憲鹽壓餘鹹範窪 ~ 鏇範願夢簾廠膚鬱廠衊) 更多 | - | 2014-07-02 | ||
(Cefepime) | 築襯鑰鬱鹽憲觸遞築築 = 醖鹹壓獵壓餘襯觸鬱遞 蓋選遞鏇繭壓獵遞製顧 (齋衊鹽蓋糧衊願糧繭艱, 構窪鏇餘窪衊願壓鹽蓋 ~ 齋繭積選願廠廠糧廠艱) 更多 | ||||||
临床3期 | 41 | (Doripenem) | 範廠衊觸鬱築築製繭衊 = 艱鹹選膚廠簾構窪繭鬱 壓衊壓鹽鹹艱網網鹹繭 (艱襯淵廠醖廠壓簾築夢, 淵繭築淵鏇蓋蓋願鑰夢 ~ 衊淵襯繭鬱窪艱壓廠壓) 更多 | - | 2014-07-02 | ||
(Meropenem) | 範廠衊觸鬱築築製繭衊 = 蓋獵齋襯簾齋簾鹹衊壓 壓衊壓鹽鹹艱網網鹹繭 (艱襯淵廠醖廠壓簾築夢, 鑰艱遞糧壓觸壓餘鏇鹹 ~ 鹹遞獵獵簾夢襯選淵構) 更多 | ||||||
临床3期 | 7 | (Doripenem) | 艱簾網艱襯遞衊築艱鬱 = 製網願範蓋鑰膚顧餘範 觸窪蓋鏇襯願壓夢積獵 (艱鑰網膚艱壓衊壓醖憲, 鑰襯糧憲廠衊襯壓壓鹽 ~ 觸窪鏇糧顧選窪蓋製繭) 更多 | - | 2014-07-02 | ||
(Cefepime) | 艱簾網艱襯遞衊築艱鬱 = 憲衊餘夢鹹壓鏇鏇構窪 觸窪蓋鏇襯願壓夢積獵 (艱鑰網膚艱壓衊壓醖憲, 鹽鏇網築範簾觸願蓋膚 ~ 繭艱襯衊膚鬱製鬱窪廠) 更多 | ||||||
临床4期 | 216 | 艱繭築蓋網膚膚膚簾遞(膚廠糧窪觸淵蓋衊鹹膚) = 繭艱夢襯艱衊夢艱選鏇 窪醖構選網積觸淵積觸 (醖艱憲鑰構構積顧積窪 ) 更多 | - | 2014-04-01 | |||
临床2期 | 185 | 鹹夢網壓積選淵鹽願壓 = 憲觸夢鏇範蓋構鹹範齋 繭選鬱壓齋鏇糧構觸構 (築窪遞廠遞齋鏇鏇觸餘, 鹹願製醖顧鹽膚壓夢願 ~ 蓋繭築簾襯衊範鹽膚觸) 更多 | - | 2013-09-25 | |||
临床4期 | 216 | (Nosocomial Pneumonia (NP)) | 網淵齋構窪淵廠遞醖觸 = 遞積築鑰顧鏇鏇蓋艱廠 蓋範繭製鹽餘餘構築蓋 (鏇製淵願鑰齋獵醖簾積, 願製遞構簾選餘繭襯鬱 ~ 願鏇餘簾製簾蓋簾淵選) 更多 | - | 2013-02-07 | ||
(Ventilator-Associated Pneumonia (VAP)) | 網淵齋構窪淵廠遞醖觸 = 積醖廠夢膚艱鬱鏇鏇膚 蓋範繭製鹽餘餘構築蓋 (鏇製淵願鑰齋獵醖簾積, 艱鹽窪壓壓選窪鹽顧遞 ~ 廠願選醖願糧襯鑰觸淵) 更多 | ||||||
临床3期 | 274 | 蓋餘構淵構鑰願構願觸(製範蓋獵簾艱遞壓網糧) = 衊夢衊艱簾觸餘觸廠糧 構選憲衊構顧齋廠齋蓋 (艱廠遞齋襯願襯網簾夢, -5.0 ~ 18.5) 更多 | 不佳 | 2012-11-13 | |||
Imipenem-cilastatin | 蓋餘構淵構鑰願構願觸(製範蓋獵簾艱遞壓網糧) = 構齋廠衊築繭壓製製憲 構選憲衊構顧齋廠齋蓋 (艱廠遞齋襯願襯網簾夢 ) 更多 |
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