Ceftriaxone: A Beta‐lactamase—stable, Broad‐spectrum Cephalosporin with an Extended Half‐life

Beam, Thomas R.

doi:10.1002/j.1875-9114.1985.tb03423.x

Cited by 32 publications

(31 citation statements)

References 134 publications

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“…Ceftriaxone, one of the third generation cephalosporins and capable of inhibiting the biosynthesis of bacterial cell wall, belongs to a group of most effective drug used as antibacterial agent. [14][15][16] Ceftriaxone is normally poorly absorbed through the mucosal membrane of the intestine and is thus ineffective when administered by the oral route. Ceftriaxone possess two negatively ionized carboxyl groups, which are responsible for high solubility and low permeability.…”

Section: Introductionmentioning

confidence: 99%

Cationic Analog of Deoxycholate as an Oral Delivery Carrier for Ceftriaxone

Lee

Kim

Lee

et al. 2005

Journal of Pharmaceutical Sciences

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Section: Introductionmentioning

confidence: 99%

Cationic Analog of Deoxycholate as an Oral Delivery Carrier for Ceftriaxone

Lee

Kim

Lee

et al. 2005

Journal of Pharmaceutical Sciences

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“…Ceftriaxone (CRO) is a widely used injectable broad-spectrum cephalosporin that exhibits potent activity against gram-positive and gram-negative bacteria (1,2,11,12). However, the therapeutic utility of ceftriaxone is limited, as it requires parenteral infusion for its administration.…”

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confidence: 99%

Pharmacokinetics of a New, Orally Available Ceftriaxone Formulation in Physical Complexation with a Cationic Analogue of Bile Acid in Rats

Lee

Kim

Lee

et al. 2006

Antimicrob Agents Chemother

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Oral administration of ceftriaxone associated with a bile acid-based new oral carrier, cholylethylenediamine, in 50% propylene glycol to rats at doses of 25 and 50 mg/kg of body weight resulted in a significant increase in intestinal absorption, as evidenced by 55% improvement in the bioavailability, whereas ceftriaxone alone showed a bioavailability of less than 1%.The introduction of new oral cephalosporins, or formulation development of existing and highly promising parenteral cephalosporins, provides a possibility for follow-up oral treatment after initial parenteral treatment, thus reducing hospitalization time and costs (5,6,14). Ceftriaxone (CRO) is a widely used injectable broad-spectrum cephalosporin that exhibits potent activity against gram-positive and gram-negative bacteria (1, 2, 11, 12). However, the therapeutic utility of ceftriaxone is limited, as it requires parenteral infusion for its administration. In this respect, the development of an oral formulation of CRO would be helpful in rapid and proper step-down therapy that would lead to better patient compliance without compromising the therapeutic activity.In a previous study, we developed a new oral delivery carrier based on bile acids, which could improve the oral bioavailability of therapeutically active peptides without damaging the tissue structure of the mucous membrane (8, 9). Based on the observation that associated bile acid could increase the absorption of a poorly absorbable drug in the intestine, we prepared a positively charged carrier by simple modification of bile acid, cholic acid, with ethylenediamine for the negatively charged small organic molecules, CRO. This scheme was designed with the goal of preparing a carrier that could physically associate with the drug by ion pair interaction to improve its lipophilicity without altering the structure of the native drug. In the present study, we show that the positively charged bile acid analogue forms a complex with CRO and report the impact of this association on the oral bioavailability.Cholylethylendiamine (CEA) was synthesized by using cholic acid and ethylenediamine as precursors. A delivery agent was composed of the hydrophobic part of bile acid and the positive charge of ethylenediamine, thereby facilitating an ionpairing interaction with anionic drug, CRO. The complex formation in aqueous medium was reversible and dependent on the molar ratio between CRO and the delivery agent. Since CRO/CEA complexes showed significantly reduced solubility in water, the lyophilized drug complex was reformulated by the addition of one of the most common water-soluble solvents, propylene glycol (PG) (15), as a prototype formulation.The partition coefficients of CRO/CEA complexes were investigated in an n-octanol/water system. CRO concentrations were analyzed on a reversed-phase high-performance liquid chromatograph (RP-HPLC) (Shimadzu, Tokyo, Japan) as previously described (3). Briefly, a 50-l aliquot of supernatant was injected into an RP-HPLC fitted with an Eclipse XDB analytical column (25...

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“…As with all other P-lactams, the antibacterial activity of ceftriaxone is due to inhibition of mucopeptide synthesis in the cell wall (2,28,32). Ceftriaxone possesses a broad spectrum of antimicrobial activity including aerobic gram-positive and gram-negative bacteria and also a few anaerobic bacteria (2,36,41). The drug is widely used in the treatment of infections caused by microorganisms resistant to conventional therapy or as an alternative to antibiotics with a low therapeutic index.…”

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Ceftriaxone protects against tobramycin nephrotoxicity

Beauchamp

Thériault

Grenier

et al. 1994

Antimicrob Agents Chemother

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The effect of ceftriaxone on tobramycin-induced nephrotoxicity was investigated. Female Sprague-Dawley rats were treated during 4 and 10 days with saline (NaCl, 0.9%), ceftriaxone at a dose of 100 mg/kg of body weight/12 h subcutaneously, tobramycin at doses of 40 and 60 mg/kg/12 h intraperitoneally, or the combination ceftriaxone-tobramycin. Creatinine levels in serum were significantly higher in animals treated with tobramycin alone given at 60 mg/kg/12 h during 10 days, compared with control animals (P < 0.01) or animals receiving the combination tobramycin-ceftriaxone (P < 0.01). After 10 days of treatment, ceftriaxone did not accumulate in renal tissue but did reduce the renal intracortical accumulation of tobramycin (P < 0.05). Tobramycin given alone at either 40 or 60 mg/kg/12 h induced a significant inhibition of sphingomyelinase activity compared with control animals (P < 0.05). However, this enzyme activity was significantly less inhibited when tobramycin was injected in combination with ceftriaxone (P < 0.05). Ceftriaxone alone had no effect on the activity of this enzyme. The [3H]thymidine incorporation into the DNA of renal cortex was also significantly lower in animals treated with tobramycin-ceftriaxone compared with animals receiving tobramycin alone (P < 0.05). The 24-h urinary excretion of 0-galactosidase was significantly reduced in animals treated with the combination tobramycin-ceftriaxone compared with the administration of tobramycin alone at 40 and 60 mg/kg/12 h after 5 and 10 days (P < 0.05). Histologically, ceftriaxone induced very few cellular alterations and reduced considerably the presence of typical signs of tobramycin nephrotoxicity. This investigation demonstrates that ceftriaxone protects animals against tobramycin-induced nephrotoxicity.

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Ceftriaxone: A Beta‐lactamase—stable, Broad‐spectrum Cephalosporin with an Extended Half‐life

Cited by 32 publications

References 134 publications

Cationic Analog of Deoxycholate as an Oral Delivery Carrier for Ceftriaxone

Cationic Analog of Deoxycholate as an Oral Delivery Carrier for Ceftriaxone

Pharmacokinetics of a New, Orally Available Ceftriaxone Formulation in Physical Complexation with a Cationic Analogue of Bile Acid in Rats

Ceftriaxone protects against tobramycin nephrotoxicity

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