Stability of meropenem and doripenem solutions for administration by continuous infusion

Berthoin, Karine; Duff, Cécile S. Le; Marchand‐Brynaert, Jacqueline; Carryn, Stéphane; Tulkens, Paul M.

doi:10.1093/jac/dkq044

Cited by 98 publications

(67 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The main works deal with the evaluation of stability in infusion solutions, using chromathographic analysis by HPLC and derivative UV spectrophotometry. [7][8][9][10] Other studies include the quantitation of doripenem in biological fluids. 11,12 For other carbapenems, the works also focus on quantitation by LC, UV spectrophotometry and microbiological assay, applied on stability studies.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the antibiotic doripenem using physicochemical methods: chromatography, spectrophotometry, spectroscopy and thermal analysis

et al. 2011

View full text Add to dashboard Cite

Recebido em 1/11/10; aceito em 14/5/11; publicado na web em 22/7/11 Doripenem was characterized through physicochemical and spectroscopic techniques, as well as thermal analysis. TLC (Rf = 0.62) and HPLC (rt = 7.4 min) were found to be adequate to identify the drug. UV and infrared spectra showed similar profile between doripenem bulk and standard. The 1 H and 13 C NMR analysis revealed chemical shifts that allowed identifying the drug. Thermal analysis demonstrated three steps with mass loss, at 128, 178 and 276 o C. The work was successfully applied to qualitative analysis of doripenem, showing the reported methods can be used for physicochemical characterization of doripenem.

show abstract

Section: Introductionmentioning

confidence: 99%

Characterization of the antibiotic doripenem using physicochemical methods: chromatography, spectrophotometry, spectroscopy and thermal analysis

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Stability of meropenem stock solution at room temperature was previously investigated by Berthoin et al 7 and, recently, by Mollà-Cantavella et al 12 No data on in vitro stability of generic meropenem drugs are available. The hospital pharmacist may have difficulty in stability data management for many injectable drugs, especially if the drugs have to be infused for long time.…”

Section: Discussionmentioning

confidence: 99%

“…For this study, the stress component for meropenem was the time. This drug is stable for a short time as demonstrated by Berthoin et al 7 who showed that carbapenems are quite unstable in concentrated (>10 mg/mL) aqueous solutions (≥10% degradation in ≤5-6 hours at 25°C). The samples were withdrawn from each bag after 72 hours and were injected in UPLC-PDA.…”

Section: Stress Testingmentioning

confidence: 94%

In Vitro Stability Evaluation of Different Pharmaceutical Products Containing Meropenem

et al. 2015

View full text Add to dashboard Cite

Background:Meropenem is a beta-lactam antibiotic for treating multidrug-resistant gram-negative bacilli infections. The expiry of the drug's patent (Merrem) allowed the production of generics to be commercialized by a few companies, including Hospira and Hikma. The stability of these medicines after reconstitution as reported on a data sheet report is 6 hours for Merrem and 1 hour for generics. Objectives: The aim of this work was to evaluate the stability profile of 3 products in 0.9% sodium chloride until 6 hours. Methods: Six polyolefin bags (2 for each drug, stored in the light and in the dark) were prepared for every test run (n =10) at concentrations of 4 and 10 mg/mL. All solutions were stored at controlled room temperature (25°C ± 3°C) and sampled immediately after preparation and at every hour until 6 hours had passed. The concentrations, pH changes, and the visual clarity were used as stability and compatibility indicators. Results: All 3 drugs retained over 95% of the initial concentration at 3 to 4 hours. At the sixth hour, all the concentrations decayed 8% to 10%. No statistical differences were observed in the percentage deviation values of the stability profile between generics and the branded drug. Conclusion:The stability profile of the products in polyolefin bags, at 4 and 10 mg/mL, was superimposable during the period of analysis and seems to show small values of deviation (1%-2%). These data do not affect the pharmacokinetics because these variations could be attributed to the intra-and interindividual variability between patients. The products showed the same stability, and consequently they could be used interchangeably in hospital pharmacy.

show abstract

“…S1 in the supplemental material for a structural model and additional modeling detail). The doripenem in vitro degradation halflife was set at 50 h for our modeling, a value determined by fitting the (10) 1 1 monoexponential decay model to the data obtained from Berthoin et al (68). The polymyxin B concentration was assumed to be constant throughout the experiments since polymyxin B is known to be stable in vitro (42).…”

Section: Methodsmentioning

confidence: 99%

Optimization of Polymyxin B in Combination with Doripenem To Combat Mutator Pseudomonas aeruginosa

Bulman

Bulitta

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

e Development of spontaneous mutations in Pseudomonas aeruginosa has been associated with antibiotic failure, leading to high rates of morbidity and mortality. Our objective was to evaluate the pharmacodynamics of polymyxin B combinations against rapidly evolving P. aeruginosa mutator strains and to characterize the time course of bacterial killing and resistance via mechanism-based mathematical models. Polymyxin B or doripenem alone and in combination were evaluated against six P. aeruginosa strains: wild-type PAO1, mismatch repair (MMR)-deficient (mutS and mutL) strains, and 7,8-dihydro-8-oxo-deoxyguanosine system (GO) base excision repair (BER)-deficient (mutM, mutT, and mutY) strains over 48 h. Pharmacodynamic modeling was performed using S-ADAPT and facilitated by SADAPT-TRAN. Mutator strains displayed higher mutation frequencies than the wild type (>600-fold). Exposure to monotherapy was followed by regrowth, even at high polymyxin B concentrations of up to 16 mg/liter. Polymyxin B and doripenem combinations displayed enhanced killing activity against all strains where complete eradication was achieved for polymyxin B concentrations of >4 mg/liter and doripenem concentrations of 8 mg/liter. Modeling suggested that the proportion of preexisting polymyxin B-resistant subpopulations influenced the pharmacodynamic profiles for each strain uniquely (fraction of resistance values are ؊8.81 log 10 for the wild type, ؊4.71 for the mutS mutant, and ؊7.40 log 10 for the mutM mutant). Our findings provide insight into the optimization of polymyxin B and doripenem combinations against P. aeruginosa mutator strains.

show abstract

Stability of meropenem and doripenem solutions for administration by continuous infusion

Cited by 98 publications

References 5 publications

Characterization of the antibiotic doripenem using physicochemical methods: chromatography, spectrophotometry, spectroscopy and thermal analysis

Characterization of the antibiotic doripenem using physicochemical methods: chromatography, spectrophotometry, spectroscopy and thermal analysis

In Vitro Stability Evaluation of Different Pharmaceutical Products Containing Meropenem

Optimization of Polymyxin B in Combination with Doripenem To Combat Mutator Pseudomonas aeruginosa

Contact Info

Product

Resources

About