Stability and degradation pattern of cefpirome (HR 810) in aqueous solution.

Sugioka, T.; Asano, Toshikazu; Chikaraishi, Yuji; Suzuki, Emi; Sano, Akimitsu; Kuriki, Takeo; Shirotsuka, Mikio; Saito, Kenji

doi:10.1248/cpb.38.1998

Cited by 31 publications

(27 citation statements)

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“…Mass spectrometry data indicated that degradation of cefepime includes cleavage of N-methylpyrrolidine (R2 side chain) and opening of the cephem (␤-lactam ring). This was the expected breakdown of cefepime, since two related compounds, ceftazidime and cefpirome, have shown similar breakdown (5,11). It also indicates that the ring opening occurs before the cleavage of N-methylpyrrolidine.…”

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confidence: 59%

Stability and Antibacterial Activity of Cefepime during Continuous Infusion

Sprauten

Beringer

Louie

et al. 2003

Antimicrob Agents Chemother

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The stability of cefepime during simulated continuous infusion was determined with a motorized portable infusion pump worn over a period of 24 to 36 h. Susceptibility testing on cefepime solutions over time indicates that the degradation products do not exhibit antibacterial activity. Cefepime stability at 24 h following continuous infusion was 94.3% ؎ 1.0%, which supports the use of continuous infusion.Continuous infusion (CI) is an efficient means of administering beta-lactams to maintain drug concentrations higher than the MIC throughout the dosing interval. Results from a number of clinical trials shows similar efficacy at a reduced dose (10,12,15). Thus, CI has a pharmacoeconomic advantage over intermittent dosing by achieving the same effect with a lower daily dose of drug (2, 6).In order to support CI of a drug, it is necessary to establish that the desired drug is stable throughout the administration period. Previous studies indicate that cefepime is stable for 24 h at room temperature (4); however, cefepime is not stable for 24 h at body temperature (13). The temperature and stability of cefepime administered with motorized portable infusion pumps are presently unknown. The purpose of this study is to determine if cefepime can be administered via CI with a motorized portable infusion pump and to define optimal conditions for storage prior to administration. In addition, the major breakdown products of cefepime will be identified and their antibacterial activity will be characterized.Methods and experimental design. The high-performance liquid chromatography procedures utilized were based on a modification of a previously published cefepime assay (3). In brief, an analytical reversed-phase C 18 column (250 by 4.6 mm; J&W Scientific) with 4.6-mm diameter particles was used to separate the various compounds found in the admixed drug solution. The column was connected onto a Hitachi L-6200 Intelligent pump, and the elutants were monitored at the cefepime absorption UV peak at 260 nm (9). The mobile phase consisted of 8% (vol/vol) acetonitrile in 20 mM ammonium acetate, adjusted to pH 4.9. The samples were kept at 4°C with a temperature-controlled water jacket. Sample concentrations were analyzed in duplicate. None of the degradation products interfered with the cefepime peak. The standard curve had a linear range from 25 to 250 g/ml, with a correlation coefficient that was Ͼ 0.999. The intraday coefficients of variation measured in triplicate ranged from 0.05 to 1.15%, and interday during the 23 analytical days ranged from 1.33 to 3.48%. The assay lower limit of detection was 25 g/ml, with a coefficient of variation of 0.54%. CI cefepime was simulated by using a portable infusion pump (Microject 30; Sorenson Medical, West Jordan, Utah). The pump and the admixed solution (MediBag, ethylene vinyl acetate, 250 ml; Sorenson Medical) were placed inside individual pouches of a light protective bag worn on a belt. The drug solution was pumped through a cassette (Microject cassette and filter; Sorenson Medical) and...

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confidence: 59%

Stability and Antibacterial Activity of Cefepime during Continuous Infusion

Sprauten

Beringer

Louie

et al. 2003

Antimicrob Agents Chemother

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“…We did not check in the present study for the release of degradation products from cefepime and cefpirome. However, the degradation of both cephalosporins has been shown to be accompanied by the release of compounds originating from their C3 substituents (namely, N-methylpyrrolidine for cefepime [12] and 6,7-dihydro-5H-1-pyrindine for cefpirome [34]). We could not find public data concerning the toxicity of these compounds.…”

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confidence: 99%

“…We could not find public data concerning the toxicity of these compounds. It is also of interest that degradation studies in water have demonstrated the destruction of the cephem ring for cefepime (28) and the release of isomers for cefpirome (epi-cefpirome, ⌬ 2 -cefpirome, and anti-cefpirome [34]). Again, no public information could be found concerning the toxicity potential of these compounds.…”

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confidence: 99%

Comparative Stability Studies of Antipseudomonal β-Lactams for Potential Administration through Portable Elastomeric Pumps (Home Therapy for Cystic Fibrosis Patients) and Motor-Operated Syringes (Intensive Care Units)

Viaene

Chanteux

Servais

et al. 2002

Antimicrob Agents Chemother

177

123

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The stability of antipseudomonal ␤-lactams in concentrated solutions was examined in view of their potential administration by continuous infusion with external pumps (for intensive care patients) or with portable pumps carried under clothing (for cystic fibrosis patients). Aztreonam (100 g/liter), piperacillin (128 g/liter, with tazobactam), and azlocillin (128 g/liter) remained 90% stable for up to more than 24 h at 37°C (mezlocillin [128 g/liter] was stable at 25°C but not at 37°C). Ceftazidime (120 g/liter), cefpirome (32 g/liter), and cefepime (50 g/liter) remained 90% stable for up to 24, 23.7, and 20.5 h at 25°C but only for 8, 7.25, and 13 h at 37°C, respectively. The control of temperature therefore appears to be critical for all three cephalosporins that cannot be recommended for use in portable pumps carried under clothes for prolonged periods for reasons of stability. Cefpirome and cefepime solutions developed an important color change (from light yellow to dark red) upon exposure when stored at 30°C or higher. Degradation of ceftazidime was accompanied by the liberation of pyridine which, at 37°C, was in excess of what is allowed by the U.S. Pharmacopeia, i.e., 1.1 mg/liter, after 8 and 12 h for drug concentrations of 12 and 8.3%, respectively. Imipenem and meropenem are too unstable (10% degradation at 25°C after 3.5 and 5.15 h, respectively) to be recommended for use by continuous infusion. Faropenem, examined in comparison with imipenem and meropenem, proved as stable as aztreonam or piperacillin.␤-Lactams are one of the most typical antibiotic classes for which the pharmacodynamic data, collected in vitro, as well as in animal studies, clearly indicate a potential advantage of a continuous infusion over the more conventional, discrete mode of administration (see references 6, 22, 23, 38, and 41 for reviews). Accordingly, several clinical trials have been initiated over the last half-decade, most notably in difficult-to-treat situations such as suspected gram-negative infections in critically ill patients (3), severe infections in intensive care patients (8,16,21,24,37), septicemia (1), severe sepsis (20), and cystic fibrosis (29,40). Yet, as clearly pointed out by one of the first promoters of the continuous infusion of ␤-lactams (6), this mode of administration, through programmable pumps or other similar devices, requires the drug to remain sufficiently stable in solution over the projected duration of the infusion. In a previous study (30), we examined the stability of ceftazidime in solution and found it to be critically dependent on the temperature within the 20 to 37°C range (68 to 99°F). This sets clear limitations on the potential use of ceftazidime by continuous infusion if administrations every 24 h are contemplated without periodic changes of the solutions. Chemical considerations suggest that the stability of the main ␤-lactams currently registered for human medicine use may vary to a meaningful extent. Unfortunately, these variations, and their consequences as far as continuous infu...

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“…With a view to create acid-stable antibiotics, cephalosporins are currently the main target of research into new anti-infection drugs [1]. It has been found that cephalosporins are vulnerable to degradation in aqueous solutions [4][5][6][7][8] and in the solid state [9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Stability of cefoselis sulfate in aqueous solutions

Zalewski

Cielecka‐Piontek

Jelińska

2012

Reac Kinet Mech Cat

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The influence of pH on the stability of cefoselis sulfate was investigated in the pH range 0.44-13.00. The degradation of cefoselis sulfate in aqueous solutions was a pseudo-first order reaction. General acid-base hydrolysis of cefoselis sulfate was observed in phosphate and acetate buffers. In solutions of hydrochloric acid, sodium hydroxide and borate buffer, k obs = k pH because only specific acidbase catalysis occurred. Specific acid-base catalysis of cefoselis sulfate involved such reactions as the hydrolysis of protonated cefoselis sulfate molecules (k 1 ), hydrolysis of cefoselis sulfate zwitter ions (k 2 ) and hydrolysis of cefoselis sulfate monoanions (k 3 ) under the influence of water. The total reaction rate was equal to the sum of partial reactions: k pH = k 1 ÁF 1

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Stability and degradation pattern of cefpirome (HR 810) in aqueous solution.

Cited by 31 publications

References 0 publications

Stability and Antibacterial Activity of Cefepime during Continuous Infusion

Stability and Antibacterial Activity of Cefepime during Continuous Infusion

Comparative Stability Studies of Antipseudomonal β-Lactams for Potential Administration through Portable Elastomeric Pumps (Home Therapy for Cystic Fibrosis Patients) and Motor-Operated Syringes (Intensive Care Units)

Stability of cefoselis sulfate in aqueous solutions

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