Cefonicid: A stable .BETA.-lactamase inhibitor.

Mehta, R. J.; Newmanb, David J.; Bowie, Betty Anne; Nash, C. H.; Actor, Paul

doi:10.7164/antibiotics.34.202

Cited by 13 publications

(7 citation statements)

References 6 publications

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“…These concentrations equal or exceed the minimal inhibitory concentration for most of the cefonicid-susceptible gram-negative bacilli and Staphylococcus aureus (1,4,6). Extrapolation of the plasma concentration-time curve indicated that a level of 1 ,g/ml would still be present in serum 24 h after the dose.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Pharmacokinetics of cefonicid, a new broad-spectrum cephalosporin

Barriere¹,

Hatheway²,

Gambertoglio³

et al. 1982

Antimicrob Agents Chemother

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This study determined the pharmacokinetic disposition of cefonicid. A single dose of 7.5 mg/kg of body weight was administered to five healthy volunteers as a 5-min intravenous infusion. Multiple plasma and urine samples were collected for 48 h. Peak plasma concentrations ranged from 95 to 156 ,ug/ml and fell slowly (mean plasma half-life, 4.4 + 0.8 h), so that levels after 12 h were in the range of 6 to 12 ,ug/ml. Urinary concentrations were high but variable and ranged from 100 to 1,000 ,ug/ml for the first 12 h after the dose and averaged 84 ,ug/ml between 12 and 24 h. Plasma and renal clearances were 0.32 ± 0.06 and 0.29 ± 0.05 ml/min per kg, respectively. An average of 88 ± 6% of the dose was excreted unchanged in the urine over 48 h. The mean steady-state volume of distribution was found to be 0.11 ± 0.01 liters/kg.More than 90% of strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, indole-positive Proteus spp., and Enterobacter spp. are inhibited by 12.5 ,ug or less of cefonicid per ml (1,6). This range of activity is at least partly explained by the relative resistance of cefonicid to hydrolysis by various beta-lactamases elicited by gram-negative organisms (6). Most strains of Serratia marcescens are resistant, as are all strains of Pseudomonas aeruginosa (4). Cefonicid is less active than cefamandole or the older cephalosporins against gram-positive cocci. However, nearly all strains of Staphylococcus aureus are inhibited by -6.25 ,ug/ml. In animal experiments, cefonicid appears to have a longer elimination half-life as compared with cefamandole or cefazolin (1). This was recently confirmed in humans (7), in whom a half-life of approximately 3.5 h was noted after intravenous or intramuscular administration. This feature and the in vitro activity of the compound make cefonicid a potentially very useful antibacterial agent. Thus, the purpose of this study was to determine the pharmacokinetic disposition of cefonicid after a single intravenous dose in healthy volunteers.MATERIALS AND METHODS Experimental procedure. Five healthy adult male volunteers participated in the study. Informed consent was obtained from each subject, and the guidelines for human experimentation of the U.S. Department of Health and Human Services and of our institution were followed in the conduct of this clinical research.A panel of laboratory tests consisting of a complete blood count, measurement of the concentration of sodium, potassium, chloride, bicarbonate, calcium, phosphate, and creatinine in serum and urea N in blood, liver function tests, urinalysis, creatinine clearance, direct Coombs test, and a complete medical history and physical examination were carried out before and after drug administration. The subjects ranged in age from 26 to 34 years and in weight from 79 to 88 kg. Creatinine clearance in the subjects averaged (± standard deviation) 117.2 ± 8.5 ml/min. Cefonicid (1,000-mg vials) was reconstituted with 2.5 ml of sterile water for injection, so that each milliliter of solution contained 330 m...

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Section: Discussionmentioning

confidence: 94%

“…are inhibited by 12.5 ,ug or less of cefonicid per ml (1,6). This range of activity is at least partly explained by the relative resistance of cefonicid to hydrolysis by various beta-lactamases elicited by gram-negative organisms (6). Most strains of Serratia marcescens are resistant, as are all strains of Pseudomonas aeruginosa (4).…”

mentioning

confidence: 99%

Pharmacokinetics of cefonicid, a new broad-spectrum cephalosporin

Barriere¹,

Hatheway²,

Gambertoglio³

et al. 1982

Antimicrob Agents Chemother

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“…and i.m. dose of cefonicid, plasma concentrations above 12 mcg/ml were sustained for 12 h : levels higher than 3 mcg/ml were maintained for 24 h after injection and were significantly higher than the 90% minimal inhibitory concentrations for most of susceptible gram-negative and gram-positive isolates (5,6).…”

Section: After Im Injection Of a Single One Gram Dose Of Cefonicidmentioning

confidence: 94%

Cross-over study of the pharmacokinetics of cefonicid administered intravenously or intramuscularly to healthy adult humans

Fourtillan¹,

Leroy²,

Lefebvre³

et al. 1985

European Journal of Drug Metabolism and Pharmacokinetics

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The pharmacokinetics of cefonicid were investigated in eight healthy adults. A one-gram dose was administered either intramuscularly or intravenously in a cross-over design study. Mean peak cefonicid plasma concentrations of 186 to 204 mcg/ml and 88 to 123 mcg/ml were achieved after intravenous and intramuscular injection, respectively, with elimination half-lives of 4.9 h and 5.3 h. Cefonicid concentrations were measured by both microbiological (M.A.) and high-performance liquid chromatography (HPLC) assays. Results were quite similar with the two techniques, except for the urinary recovery of cefonicid in the first 24 hours (83% of the dose with MA - vs 53% with HPLC method). The apparent volume of distribution (Vd area) was 0.18 1/kg; the total body clearance (CT) and the renal clearance (CR) were 24-26 ml/min and 15-19 ml/min, respectively. The kinetic data of cefonicid were not significantly different for the two routes of administration. A one-gram i.v. or i.m. cefonicid dose produced high and prolonged plasma concentrations with a longer half-life than obtained with commonly used cephalosporins.

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“…5 Forty pediatric and adult patients were randomized to receive either intravenous cefuroxime 50-75 mg/kg q8h or ampicillin 38-75 mg/kg q6h plus chloramphenicol 50-100 mg/kg/d for at least five days. The most prevalent pathogen was H. influenzae, including…”

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confidence: 99%

Inappropriate Use of High-Dose Glyburide to Treat Uncontrolled Type 2 Diabetes Mellitus

1993

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The new second-generation cephalosporins, cefonicid, ceforanide, and cefuroxime, have recently become available. These agents are generally less active against gram-positive cocci than first-generation cephalosporins and, at best, equal to cefoxitin and cefamandole against many gram-negative bacteria. Cefuroxime, however, is the most active cephalosporin for {3lactamase-producing Haemophilus influenzae. These newer agents have superior pharmacokinetic characteristics over cefoxitin and cefamandole. Smaller doses, longer dosing intervals and, potentially, a reduction in total drug cost may be the real advantage of these agents. Open trials and a limited number of comparative studies have documented the effectiveness of cefonicid, ceforanide, and cefuroxime in the treatment of most mild-to-serious infectious diseases, although failures with cefonicid in the treatment of staphylococcal infections have been reported. Notably, cefuroxime has received approval for the treatment of common pediatric bacterial meningitis infections. Replacement of cefamandole or cefoxitin with one of these "longer-acting" agents may be cost-beneficial; however, clinicians must be on alert for the development of bacterial resistance or decreased efficacy.

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Cefonicid: A stable .BETA.-lactamase inhibitor.

Cited by 13 publications

References 6 publications

Pharmacokinetics of cefonicid, a new broad-spectrum cephalosporin

Pharmacokinetics of cefonicid, a new broad-spectrum cephalosporin

Cross-over study of the pharmacokinetics of cefonicid administered intravenously or intramuscularly to healthy adult humans

Inappropriate Use of High-Dose Glyburide to Treat Uncontrolled Type 2 Diabetes Mellitus

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