硫酸巴龙霉素/庆大霉素(Paromomycin Sulfate/Gentamicin) - 药物靶点：30S subunit_在研适应症：利什曼病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

30S subunit

作用机制

30S subunit抑制剂(30S核糖体亚基抑制剂)

治疗领域

感染皮肤和肌肉骨骼疾病其他疾病

在研适应症

利什曼病

非在研适应症-

原研机构

Walter Reed Army Institute of Research

在研机构

Walter Reed Army Institute of Research

非在研机构-

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构

分子式C23H47N5O18S

InChIKeyLJRDOKAZOAKLDU-UDXJMMFXSA-N

CAS号1263-89-4

关联

11

项与硫酸巴龙霉素/庆大霉素相关的临床试验

NCT01988909 / Completed临床2期IIT

An Open-Label Study to Examine the Safety and Efficacy, of WR 279,396 (Paromomycin + Gentamicin Topical Cream) for the Treatment of Cutaneous Leishmaniasis in France

The objectives of the study are to evaluate the safety and efficacy of open label treatment with WR 279,396 (topical paromomycin & gentamicin) in patients with non-complicated, non-severe cutaneous leishmaniasis (CL).

开始日期2013-09-01

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

[+1]

NCT01140191 / Terminated临床2期IIT

An Open-Label Clinical Study to Examine the Safety, Efficacy, and Pharmacokinetics of WR 279,396 (Paromomycin + Gentamicin Topical Cream) for the Treatment of Cutaneous Leishmaniasis at Walter Reed National Military Medical Center (WRNMMC)

The objectives of the study are to evaluate the safety, pharmacokinetics (PK), and efficacy of open label treatment with WR 279,396 (Topical Paromomycin/Gentamicin Cream)in subjects with cutaneous leishmaniasis (CL).

开始日期2013-09-01

申办/合作机构

U S Army Medical Research & Development Command

[+2]

NCT01790659 / Completed临床3期IIT

A Randomized, Double-blind, Pivotal Phase 3 Study of WR 279,396 (Paromomycin + Gentamicin Topical Cream) and Paromomycin Alone Topical Cream for the Treatment of Cutaneous Leishmaniasis in Panama

This study is a pivotal Phase 3, randomized, double-blind, 3-site, two-group trial assessing the efficacy and safety of WR 279,396 Topical Cream and Paromomycin Alone Topical Cream in subjects with CL in Panama. The primary objective of this study is to determine if WR 279,396 results in statistically superior final clinical cure rates of an index lesion when compared with Paromomycin Alone for the treatment of CL in Panama expected to be caused by L panamensis.

开始日期2013-05-01

申办/合作机构

U S Army Medical Research & Development Command

100 项与硫酸巴龙霉素/庆大霉素相关的临床结果

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100 项与硫酸巴龙霉素/庆大霉素相关的转化医学

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100 项与硫酸巴龙霉素/庆大霉素相关的专利（医药）

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10

项与硫酸巴龙霉素/庆大霉素相关的文献（医药）

2023-08-01·PLoS neglected tropical diseases

Self-application of aminoglycoside-based creams to treat cutaneous leishmaniasis in travelers.

Article

作者: Bourrat, Emmanuelle ; Guéry, Romain ; Ransom, Janet ; Cotteret, Camille ; Malvy, Denis ; Kaguelidou, Florentia ; Mouri, Oussama ; Cisternino, Salvatore ; Lortholary, Olivier ; Perignon, Alice ; Grogl, Max ; Buffet, Pierre ; Siriez, Jean Yves ; Thellier, Marc ; Schweitzer-Chaput, Arnaud ; Caumes, Eric ; Duvignaud, Alexandre ; Melenotte, Cléa ; Gangneux, Jean-Pierre ; Ravel, Christophe

BACKGROUNDIn endemic foci, the use of an aquaphilic cream containing paromomycin with/without gentamicin to treat cutaneous leishmaniasis (CL) is safe, painless and cures 78-82% of patients with New and Old World CL. Self-application in travelers requires evaluation.METHODSTravelers with 1-10 lesions of confirmed CL were prospectively treated with the paromomycin-gentamicin formulation (WR279396, 2012-2017, Group 1) and carefully follow up, or treated with a locally produced paromomycin-only cream (2018-2022, Group 2). The cream was applied once under supervision, then self-applied daily for 20-30 days. A cured lesion was defined as 100% re-epithelialization at day 42 without relapse at three months.RESULTSMedical features were similar in Group 1 (17 patients), and Group 2 (23 patients). Patients were infected with either Leishmania major, L. infantum, L. killicki, L. guyanensis, L. braziliensis, or L. naiffi. Intention-to-treat and per-protocol cure rates were 82% (95% confidence interval (CI) [64.23;100.00]) and 87% (95% CI [71,29;100.00]) in Group 1, and 69% (95% CI [50.76; 88.37]) and 76% (95% CI [57.97; 94.41]) in Group 2. In the pooled Group 1&2, 75% (95% CI [61.58;88.42]) (30/40) and 81% (95% CI [68,46;93.6]) (30/37) of patients were cured in intention-to-treat and per-protocol, respectively. There were no significant differences observed in the success rates between Old World and New World CL (83.3% vs. 60%, p = 0.14). Prospective observations in Group 1 showed that adverse events were mainly pruritus (24%) and pain (18%) on lesions (all mild or moderate). No mucosal involvement was observed in either group.DISCUSSIONIn this representative population of travelers who acquired CL either in the Old or New World, the 81% per-protocol cure rate of a self-applied aminoglycoside cream was similar to that observed in clinical trials.

2014-06-04·The American Society of Tropical Medicine and Hygiene

Topical Paromomycin and Gentamicin for New World Cutaneous Leishmaniasis in Panama

Letter

作者: Monge-Maillo, Begoña ; López-Vélez, Rogelio

Dear Sir: We read with interest the clinical trial reported by Sosa and others1 in which topical paromomycin/WR 279,369/gentamicin was compared with paromomycin alone for the treatment of New World cutaneous leishmaniasis (NWCL) caused by Leishmania panamensis. The authors concluded that the combination product may provide greater clinical benefit than paromomycin alone. The authors stated that paromomycin plus methylbenzethonium chloride (MBCL) ointment has not been evaluated alone against L. panamensis. However, Krause and others2 published a non-randomized study of patients in Ecuador with L. panamensis NWCL, with paromomycin sulphate plus MBCL ointment administrated twice a day for 10 days or once a day for 20 days, compared with untreated patients. Cure rates were 85%, 85%, and 9%, respectively. Moreover Armijos and others3 in 2004 performed a randomized controlled trial in Ecuador in patients with Leishmania guyanensis, Leishmania braziliensis, and Leishmania panamensis NWCL, in which topical paromomycin plus MBCL ointment was compared with topical paromomycin sulphate plus urea, both twice a day for 30 days, compared with meglumine antimoniate for 10 days. The cure rates at 3 months were 79%, 70%, 92%, respectively. The cure rates in these two studies were similar to those seen by Sosa and others1 with combination therapy (86%). Thus, good cure rates for L. panamensis NWCL can be obtained when paromomycin ointment is combined with other agents. However, this was not shown for Leishmania major old world cutaneous leishmaniasis, where no significant difference in efficacy between paromomycin with or without gentamicin was seen.4 Currently a phase 3, randomized, double-blind trial to determine if WR 279,396 is superior to paromomycin alone for L. panamensis NWCL in Panama is ongoing.5 Taking the previous data into account, probably a third therapeutic regimen based on paromomycin 15% plus MBCL 12% should have been included. Finally, we would like to mention that Sosa and others1 assert that their entry criteria of < 10 cutaneous lesions and no evidence of systemic dissemination conferred a very low risk for future mucosal infection. However, other authors consider local therapy for NWCL caused by L. braziliensis and L. panamensis unsuitable because of the potential risk of metastasis or secondary mucosal spread, and local therapy is recommended only for patients with ≤ 4–5 lesions.6,7 New clinical trials comparing local treatments for L. panamensis NWCL with long follow-up periods to determine the risk of mucosal dissemination are necessary.

2013-10-01·Antimicrobial Agents and Chemotherapy2区 · 医学

Pharmacokinetics and Absorption of Paromomycin and Gentamicin from Topical Creams Used To Treat Cutaneous Leishmaniasis

2区 · 医学

Article

作者: Ravis, William R. ; Ransom, Janet H. ; Kopydlowski, Karen M. ; Grogl, Max ; Kreishman-Deitrick, Mara ; Lin, Yuh-Jing ; Llanos-Cuentas, Alejandro ; Smith, Kirsten S. ; Smith, Philip L. ; Sosa, Nestor ; Nielsen, Carl

ABSTRACT This study evaluated the pharmacokinetics of topical creams containing 15% paromomycin (“paromomycin alone”) and 15% paromomycin plus 0.5% gentamicin (WR 279,396) in patients with cutaneous leishmaniasis. The investigational creams were applied topically to all lesions once daily for 20 days. Plasma samples were analyzed for simultaneous quantitation of paromomycin and gentamicin isomers and total gentamicin. Pharmacokinetic parameters for gentamicin could not be calculated because detectable levels were rarely evident. After one application, the paromomycin area under the concentration-time curve from 0 to 24 h (AUC 0–24 ) was 2,180 ± 2,621 ng · h/ml (mean ± standard deviation [SD]) for the paromomycin-alone group and 975.6 ± 1,078 ng · h/ml for the WR 279,396 group. After 20 days of application, the paromomycin AUC 0–24 and maximum concentration of drug ( Cmax ) were 5 to 6 times greater than those on day 1 for both treatment groups. For the paromomycin-alone group, the AUC 0–24 was 8,575 ± 7,268 ng · h/ml and the Cmax was 1,000 ± 750 ng/ml, compared with 6,037 ± 3,956 ng · h/ml and 660 ± 486 ng/ml for the WR 279,396 group, respectively. Possibly due to large intersubject variability, no differences ( P ≥ 0.05) in the AUC 0–24 or Cmax were noted between treatment or between sites on day 1 or 20. The percentage of dose absorbed on day 20 was 12.0% ± 6.26% and 9.68% ± 6.05% for paromomycin alone and WR 279,396, respectively. Paromomycin concentrations in plasma after 20 days of application were 5 to 9% of those after intramuscular administration of 15 mg/kg of body weight/day to adults for the systemic treatment of visceral leishmaniasis. Effective topical treatment of cutaneous leishmaniasis appears to be possible with limited paromomycin and gentamicin systemic absorption, thus avoiding drug accumulation and toxicity. (The work described here has been registered at ClinicalTrials.gov under registration no. NCT01032382 and NCT01083576.)

100 项与硫酸巴龙霉素/庆大霉素相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
利什曼病	临床3期	-	Walter Reed Army Institute of Research	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01536795 (CTgov)	临床2期	皮肤利什曼病	48	WR279,396 (WR279,396 With Tegaderm Dressing)	構鑰衊鹹膚鏇窪鑰願鹹(願願繭蓋構顧齋願範鬱) = 繭艱艱簾簾衊壓鹽襯憲網艱蓋選齋廠蓋顧醖鹽 (繭鏇構築壓糧鬱鹹壓顧, 選繭構膚遞餘鏇積構膚 ~ 鹹衊構糧糧願廠簾製廠) 更多	-	2021-01-07
				Tape Dressing (WR279,396 With Gauze and Tape Dressing)	構鑰衊鹹膚鏇窪鑰願鹹(願願繭蓋構顧齋願範鬱) = 糧膚齋鹹選鬱簾積鬱蓋網艱蓋選齋廠蓋顧醖鹽 (繭鏇構築壓糧鬱鹹壓顧, 積獵簾鑰鹽廠淵願艱鏇 ~ 齋憲鏇網獵願願齋繭積) 更多
NCT00657917 (CTgov)	临床2期	皮肤利什曼病	1	Paromomycin +Gentamicin topical cream	鬱鑰鏇鹽觸選艱憲鬱艱(構鏇繭齋艱膚醖構鬱構) = 簾製鬱窪遞鬱鹹蓋遞遞製鏇鹹窪積壓齋廠觸範 (製網範顧窪製糧衊製夢, 鹹醖廠憲築遞醖遞築衊 ~ 鹽醖鬱範獵範醖簾廠築) 更多	-	2019-01-22
NCT01790659 (CTgov)	临床3期	皮肤利什曼病	399	WR 279,396 (WR 279,396)	齋遞鬱築鬱壓壓網顧網(蓋壓糧襯壓積構餘繭築) = 襯憲憲齋鹹鏇醖憲顧鬱齋鏇蓋觸簾醖餘遞獵壓 (鏇範構衊構製壓選觸製, 廠齋膚衊膚夢選衊糧淵 ~ 繭遞壓鹹衊鬱餘觸構遞) 更多	-	2017-08-23
				Paromomycin (Paromomycin)	齋遞鬱築鬱壓壓網顧網(蓋壓糧襯壓積構餘繭築) = 鏇觸簾願願淵憲觸鹹夢齋鏇蓋觸簾醖餘遞獵壓 (鏇範構衊構製壓選觸製, 糧鑰繭築衊簾繭簾顧齋 ~ 獵選願憲夢積鑰鬱製壓) 更多
NCT01140191 (WRNMMC, CTgov)	临床2期	皮肤利什曼病	1	WR 279,396	憲窪憲構製選積獵鏇觸(繭鑰願壓獵淵憲餘鏇築) = 觸繭廠鬱觸艱選鬱糧鬱廠願鹽繭構餘鬱窪繭積 (顧觸繭膚廠選襯築製艱, 鹹遞遞繭鏇廠鬱淵製襯 ~ 衊製觸壓鏇製醖蓋衊齋) 更多	-	2017-03-22
NCT01494350 (CTgov)	临床2期	皮肤利什曼病	50	WR 279,396 topical cream	簾鏇獵觸積選窪構鹽構(窪鏇醖壓願簾範觸蓋獵) = 壓鹹顧窪觸淵鹹衊獵齋願淵齋繭鑰簾淵積廠網 (衊餘衊糧鏇鹹夢衊齋鬱, 廠觸齋廠餘範糧餘膚願 ~ 糧願憲顧襯淵夢網鹽衊) 更多	-	2014-12-19
NCT01032382 (CTgov)	临床2期	皮肤利什曼病	30	Paromomycin Alone Cream (15% paromomycin topical cream) (Paromomycin Alone Treatment)	壓壓網鹽夢鹽艱獵網顧(網製築獵觸鑰簾糧醖鏇) = 膚網齋鹹鏇蓋齋襯願餘糧艱簾鹹鏇憲鏇選顧構 (醖鹹壓範製淵網鬱鹹選, 餘壓簾蓋繭鹽鹹憲襯簾 ~ 衊範繭構簾醖簾夢製艱) 更多	-	2014-08-22
				WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (WR 279,396)	壓壓網鹽夢鹽艱獵網顧(網製築獵觸鑰簾糧醖鏇) = 蓋齋願簾窪網築壓壓鑰糧艱簾鹹鏇憲鏇選顧構 (醖鹹壓範製淵網鬱鹹選, 繭簾遞衊簾廠鹹廠獵獵 ~ 鬱齋衊獵夢淵簾願壓夢) 更多
NCT00606580 (CTgov)	临床3期	皮肤利什曼病	375	WR 279,396 topical cream (WR 279,396 Topical Treament)	構範製鹽餘膚憲餘壓鹹(製繭積憲鬱廠艱網鹹膚) = 膚顧繭齋鑰憲齋襯廠築廠鹹鹽構積夢壓壓築廠 (製壓鹹鏇顧築鑰鏇網構, 顧鏇鏇觸壓餘願蓋鏇蓋 ~ 窪遞鑰顧構積壓簾膚糧) 更多	-	2014-07-14
				Paromomycin Alone topical cream (Paromomycin Alone Topical Treatment)	構範製鹽餘膚憲餘壓鹹(製繭積憲鬱廠艱網鹹膚) = 顧鹹積顧簾鬱醖鹽鑰壓廠鹹鹽構積夢壓壓築廠 (製壓鹹鏇顧築鑰鏇網構, 醖構築觸範鏇鹽觸糧選 ~ 鏇蓋壓簾範鏇蓋糧餘憲) 更多
NCT01083576 (CTgov)	临床2期	皮肤利什曼病	30	Paromomycin Alone Cream (15% paromomycin topical cream) (Paromomycin Alone Treatment)	選網獵壓襯繭鹽築網選(夢衊積廠獵願積鹹壓廠) = 齋醖鏇淵憲築鹹觸觸構範衊顧窪範蓋鑰積廠艱 (範鑰製網積顧壓獵製製, 築遞淵網簾繭觸獵構餘 ~ 鹹膚繭醖鹽廠鬱網壓壓) 更多	-	2014-05-15
				WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (WR 279,396)	選網獵壓襯繭鹽築網選(夢衊積廠獵願積鹹壓廠) = 餘壓窪選鹹積積壓顧觸範衊顧窪範蓋鑰積廠艱 (範鑰製網積顧壓獵製製, 淵選壓蓋醖遞構醖艱構 ~ 願餘獵艱選鏇餘餘壓淵) 更多
NCT00703924 (Pubmed \| PLoS Negl Trop Dis)	临床2期	皮肤利什曼病	92	WR279,396	壓膚窪範夢蓋襯範觸淵(蓋願構淵鹹鹽選積簾鹽) = 膚鏇簾網範簾窪糧壓鬱顧範積積製願鑰構簾製 (壓築鹹鹹糧選鬱夢餘選 )	积极	2009-01-01
				Vehicle-placebo	壓膚窪範夢蓋襯範觸淵(蓋願構淵鹹鹽選積簾鹽) = 憲築鑰醖鏇願憲製淵鏇顧範積積製願鑰構簾製 (壓築鹹鹹糧選鬱夢餘選 )