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Last update 09 Dec 2025
Doripenem
Last update 09 Dec 2025
Overview
Basic Info
Drug Type Small molecule drug |
Synonyms Doripenem Hydrate, Doripenem hydrate (JP17), doripenem monohydrate + [9] |
Target |
Action inhibitors |
Mechanism PBPs inhibitors(Bacterial penicillin-binding protein inhibitors) |
Therapeutic Areas |
Active Indication |
Inactive Indication |
Originator Organization |
Active Organization |
Inactive Organization |
License Organization |
Drug Highest PhaseApproved |
First Approval Date Japan (25 Jul 2005), |
RegulationOrphan Drug (United States) |
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Structure/Sequence
Molecular FormulaC15H26N4O7S2 |
InChIKeyNTUBEBXBDGKBTJ-WGLOMNHJSA-N |
CAS Registry364622-82-2 |
Related
50
Clinical Trials associated with DoripenemCTR20180182
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
[Translation] Single-dose pharmacokinetics and pharmacokinetic/pharmacodynamic studies of doripenem for injection in healthy subjects
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
[Translation] A randomized, blinded, positive drug parallel controlled, multicenter clinical study to evaluate the efficacy and safety of doripenem for injection in the treatment of patients with complicated urinary tract infection
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
[Translation] A randomized, blinded, parallel-controlled, multicenter trial of meropenem for injection to evaluate the safety and efficacy of doripenem for injection in the treatment of complicated urinary tract infections
100 Clinical Results associated with Doripenem
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100 Translational Medicine associated with Doripenem
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100 Patents (Medical) associated with Doripenem
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1,544
Literatures (Medical) associated with Doripenem01 Oct 2025YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
Clinical Pharmacological Research Aiming to Optimize Therapeutic Strategies in Specific Populations
Review
Author: 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.
05 Aug 2025Microbiology Spectrum
Specific variants in
ftsI
reduce carbapenem susceptibility in
Pseudomonas aeruginosa
Article
Author: 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.
01 Aug 2025MICROBIAL PATHOGENESIS
Inhibitory effect of naringin, naringenin, and crocin on biofilm formation and lecA gene expression in Pseudomonas aeruginosa clinical isolates
Article
Author: Goli, Hamid Reza ; Gholami, Mehrdad ; Sherafati, Sara ; Ebrahimzadeh, Mohammad Ali
Biofilm formation by Pseudomonas aeruginosa is a considerable challenge in treating infections. We aimed to investigate the inhibitory effect of crocin, naringin, and naringenin on biofilm formation capacity and the expression of the lecA gene by this organism. One hundred unrepeated P. aeruginosa isolates were collected from hospitalized patients and were identified. The antibiotic resistance pattern of the isolates was determined using the disk agar diffusion method. The minimum inhibitory concentration (MIC) of naringin, naringenin, and crocin was determined by a micro broth dilution test. Then, the biofilm production ability of the isolates was evaluated before and after treatment with the investigated flavonoids using the microtiter plate test. Finally, the lecA gene expression of the isolates was checked before and after treatment with investigated flavonoids using the Real-time PCR method. Among 89 biofilm-producer isolates, 48 (53.93 %), 17 (19.1 %), and 24 (26.96 %) showed a strong, moderate, and weak biofilm formation ability. Biofilm-positive isolates were more resistant to all tested antibiotics. Also, among 41 multidrug-resistant (MDR) isolates, 33 (80.48 %) were strong biofilm producers (P-value = 0.01). A strong correlation was observed between the lecA gene expression and the biofilm production ability of the isolates (P-value = 0.000). The investigated flavonoids were significantly effective on biofilm production by P. aeruginosa. Among 10 strong-biofilm producers, all (100 %) showed a moderate ability to form biofilm after treatment with crocin (P-value = 0.02), and 6 (60 %) isolates had lost their ability to produce biofilm after treatment with the simultaneous use of crocin with ciprofloxacin or tobramycin (P-value = 0.000). Also, one isolate was grouped as biofilm-negative after treatment with naringin (P-value = 0.012). The crocin, naringin, and naringenin and their concurrent use of antibiotics decreased 2-8-fold of the lecA gene expression in strong biofilm-producer isolates (P-value˂0.05). Crocin, naringin, and naringenin can be used separately or simultaneously with antibiotics to inhibit biofilm and reduce the expression of virulence factors effective in biofilm production in P. aeruginosa.
2
News (Medical) associated with Doripenem100 Deals associated with Doripenem
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R&D Status
Approved
10 top approved records. to view more data
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| Indication | Country/Location | Organization | Date |
|---|---|---|---|
| Meningococcal Infections | Japan | 17 Mar 2015 | |
| Paediatric infections | Japan | 10 Apr 2013 | |
| Hospital-acquired pneumonia | European Union | 25 Jul 2008 | |
| Hospital-acquired pneumonia | Iceland | 25 Jul 2008 | |
| Hospital-acquired pneumonia | Liechtenstein | 25 Jul 2008 | |
| Hospital-acquired pneumonia | Norway | 25 Jul 2008 | |
| Pneumonia, Ventilator-Associated | European Union | 25 Jul 2008 | |
| Pneumonia, Ventilator-Associated | Iceland | 25 Jul 2008 | |
| Pneumonia, Ventilator-Associated | Liechtenstein | 25 Jul 2008 | |
| Pneumonia, Ventilator-Associated | Norway | 25 Jul 2008 | |
| Complicated intra-abdominal infection | United States | 12 Oct 2007 | |
| Complicated urinary tract infection | United States | 12 Oct 2007 | |
| Pyelonephritis | United States | 12 Oct 2007 | |
| Gram-Negative Bacterial Infections | Japan | 08 Sep 2005 | |
| Gram-Positive Bacterial Infections | Japan | 03 Sep 2005 | |
| Urinary Tract Infections | Japan | 30 Aug 2005 | |
| Bacterial Infections | Japan | 25 Jul 2005 | |
| Respiratory Tract Infections | Japan | 25 Jul 2005 |
Developing
10 top R&D records. to view more data
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| Indication | Highest Phase | Country/Location | Organization | Date |
|---|---|---|---|---|
| Abdomen, Acute | Phase 3 | United States | 01 Dec 2010 | |
| Abdomen, Acute | Phase 3 | Argentina | 01 Dec 2010 | |
| Abdomen, Acute | Phase 3 | Brazil | 01 Dec 2010 | |
| Abdomen, Acute | Phase 3 | Chile | 01 Dec 2010 | |
| Abdomen, Acute | Phase 3 | Colombia | 01 Dec 2010 | |
| Abdomen, Acute | Phase 3 | Latvia | 01 Dec 2010 | |
| Abdomen, Acute | Phase 3 | Lithuania | 01 Dec 2010 | |
| Abdomen, Acute | Phase 3 | Panama | 01 Dec 2010 | |
| Abdominal Abscess | Phase 3 | United States | 01 Dec 2010 | |
| Abdominal Abscess | Phase 3 | Argentina | 01 Dec 2010 |
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Clinical Result
Clinical Result
Indication
Phase
Evaluation
View All Results
Phase 3 | - | 13 | Doripenem 1 g q8h | ymlczohslc(qolcllvakw) = wxbmvtivgx jesbokbixm (sodvxvvgse ) View more | - | 28 Dec 2015 | |
NCT01381848 (Pubmed) Manual  | Phase 1 | 52 | (Neonates (<4 weeks in chronological age)) | hdrmfsheqd(hhfrqnpede) = rbrdekzaky eycfyhoesn (jcvwsncvmh ) View more | Positive | 01 Aug 2015 | |
(infants >4 weeks.) | hdrmfsheqd(hhfrqnpede) = qfxehrxiaq eycfyhoesn (jcvwsncvmh ) View more | ||||||
Not Applicable | Febrile Neutropenia First line | - | qgenqrnspg(hsbnlyqufz) = rxcgysgrck rcvgdhtmgr (cyumalwinh ) View more | Positive | 21 May 2015 | ||
qgenqrnspg(hsbnlyqufz) = onvzcxtlbs rcvgdhtmgr (cyumalwinh ) View more | |||||||
Phase 3 | 41 | (Doripenem) | kxnhjmuxqs = mlfxchpcow bwpxezobme (bwppkfuhjt, rysfmfpjad - fyzxzbzjka) View more | - | 02 Jul 2014 | ||
(Meropenem) | kxnhjmuxqs = cuvbrfmfjs bwpxezobme (bwppkfuhjt, lmzonfsidd - aiwtxukdwm) View more | ||||||
Phase 3 | 7 | (Doripenem) | lnxbffylby = evmjpfpeqi wxukcxgozm (vlefszkjna, vhwoekkscq - xuqbpjuath) View more | - | 02 Jul 2014 | ||
(Cefepime) | lnxbffylby = lucvcujoti wxukcxgozm (vlefszkjna, mvqnoptdim - vizxtqcciq) View more | ||||||
Phase 3 | 41 | (Doripenem) | bfhequelwu = rljftbvted psfxllcvhv (gkygxqjknx, cncvzxwvuh - mgzydvxyic) View more | - | 02 Jul 2014 | ||
(Cefepime) | bfhequelwu = pgowyteniw psfxllcvhv (gkygxqjknx, rvpoekmybp - zphbppntkl) View more | ||||||
Phase 4 | 216 | qdofavkjid(cgdciofgyg) = zbaimjymge vwfwjlbfrx (bnxeogjqsm ) View more | - | 01 Apr 2014 | |||
Phase 2 | 185 | hjmgosnduk = xgmhpxeahc ztixxkvplz (oixwofbnqd, cwelpkfngx - rutogljmrf) View more | - | 25 Sep 2013 | |||
Phase 4 | 270 | (Nosocomial Pneumonia) | qmzrpvttfu = ujapgzgyiu vunpgzlpsv (rpimsecton, rhbkjpqolk - olkyztbirc) View more | - | 28 Aug 2013 | ||
(Complicated Intra-Abdominal Infections) | qmzrpvttfu = bgmvutauia vunpgzlpsv (rpimsecton, fqmyisipls - ypieocbbuu) View more | ||||||
Phase 4 | 216 | (Nosocomial Pneumonia (NP)) | jfgcqxfzgk = vdktgytkmg tuqwjkvoew (zcmwwjfmcr, zktwsmozcx - tyrohvyahh) View more | - | 07 Feb 2013 | ||
(Ventilator-Associated Pneumonia (VAP)) | jfgcqxfzgk = cokxmjbktr tuqwjkvoew (zcmwwjfmcr, ivjkpfmtgv - aqvlgucecn) View more |
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