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PubMed1982

Comparative trial of cefonicid and cefamandole in the therapy of community-acquired pneumonia.

Cefonicid (Smith Kline & French Laboratories; D-75073) is a new parenteral cephalosporin with a markedly long half-life, high serum levels, and good in vitro activity against Haemophilus influenzae. Patients with community-acquired pneumonia were randomized 2:1 to receive cefonicid, 1 g daily (21 cases) or cefamandole, 1 g every 6 h (12 cases). The two groups were similar, except that the cefonicid patients were older (mean 42 versus 31 years). Peak serum levels of cefonicid averaged 133 microgram/ml after intravenous and 83 microgram/ml after intramuscular administration compared with 55 microgram/ml with intravenous cefamandole. All 9 patients on intramuscular cefonicid and 8 or 12 patients on intravenous cefonicid had trough serum levels of greater than 2.0 microgram/ml at 24 h. Sputum levels of cefonicid were usually between 2.0 and 4.0 microgram/ml and did not correlate with serum levels. Cefonicid was well tolerated, and all cefonicid patients responded clinically. Sputum cultures for H. influenzae or Streptococcus pneumoniae became negative in 6 of 7 cefamandole patients and 13 or 15 cefonicid patients. In in vitro studies, cefonicid inhibited 90% of beta-lactamase-negative h. influenzae at 0.5 microgram/ml and beta-lactamase-positive strains at 2.0 microgram/ml. Cefonicid inhibited 50% of S. pneumoniae at 1.6 microgram/ml, but required 6.4 microgram/ml to inhibit 90%. Cefonicid once a day appears to be as safe and as effective as cefamandole four times a day for therapy of community-acquired pneumonia.

Adult↗

PubMedDate not supplied

Review of cefonicid, a long-acting cephalosporin.

The in vitro activity, pharmacokinetics, adverse effects, and clinical efficacy of cefonicid are reviewed. Also discussed are formulary considerations and bacterial resistance. Cefonicid, an investigational agent near approval, is less active than other currently available first- and second-generation cephalosporins against gram-positive cocci, particularly Staphylococcus. Cefonicid and cefamandole have similar activity that is superior to the first-generation cephalosporins against Escherichia coli, Klebsiella, Citrobacter spp., Enterobacter spp., indole-negative Proteus spp., and Providencia spp. Organisms such as Serratia marcescens, Acinetobacter, Pseudomonas, and Bacteroides fragilis are resistant to cefonicid. Despite a small volume of distribution and high protein binding, cefonicid achieves high tissue concentrations. Approximately 90% of an administered dose is excreted unchanged in the urine, and the elimination half-life is approximately four hours. Cefonicid is usually well tolerated. In treating skin infections, cefonicid was usually less effective than cefazolin against Staphylococcus aureus. In genitourinary infections, cefonicid 1 g daily (as the sodium salt) in a single dose has shown comparable efficacy to cefamandole or amoxicillin given in multiple daily doses. Based on available data, single daily dosing of cefonicid in the therapy of Staph. aureus endocarditis is not effective. In studies of patients undergoing hysterectomy, cesarean section, cholecystectomy, and colorectal surgery, cefonicid 1 g given as a single preoperative dose has produced results comparable with those of cefoxitin 1-2 g (as the sodium salt) given preoperatively and for several doses postoperatively. The major clinical uses of cefonicid will probably be as a possible cost-reducing alternative (based on a single daily dose) to currently available first- and second-generation cephalosporins for the treatment of community-acquired pneumonia and infections caused by enteric organisms. It may also be useful as a possible cost-reducing alternative to cefoxitin for prophylaxis in hysterectomy and biliary tract surgery.

Bacterial Infections↗

PubMed1993

Randomized trial comparing ceftriaxone with cefonicid for treatment of spontaneous bacterial peritonitis in cirrhotic patients.

We compared cefonicid (2 g every 12 h) and ceftriaxone (2 g every 24 h) for their efficacy and safety in treating spontaneous bacterial peritonitis in cirrhotic patients in an open randomized clinical trial (30 patients in each group). Clinical, laboratory, and bacteriologic characteristics were similar in both groups. Ceftriaxone-susceptible strains were isolated on 44 occasions (94%), and cefonicid-susceptible strains were isolated on 43 occasions (91.5%). The antibiotic concentration in ascitic fluid/MIC ratio for ceftriaxone was > 100 throughout the dose interval (24 h), while it was lower for cefonicid (between 1 and 18). A total of 100% of patients treated with ceftriaxone, and 94% of those treated with cefonicid were cured of their infections (P was not significant). Hospitalization mortality was 37% in the cefonicid group and 30% in the ceftriaxone group (P was not significant). The time that elapsed between the initiation of treatment and the patient's death was shorter in the cefonicid group patients (5.3 +/- 3.90 days) than in the ceftriaxone group patients (11.8 +/- 9.15 days) (P < 0.05). None of the patients presented with superinfections, and only two patients treated with cefonicid and three patients treated with ceftriaxone developed colonizations with Enterococcus faecalis or Candida albicans. Ceftriaxone and cefonicid are safe and useful agents for treating cirrhotic spontaneous bacterial peritonitis, although the pharmacokinetic characteristics of ceftriaxone seem to be more advantageous than those of cefonicid.

Aged↗

PubMed1985

High-performance liquid chromatographic determination of cefonicid in human plasma and urine.

A high-performance liquid chromatographic assay for determination of cefonicid concentrations in human plasma and urine samples has been developed using cefazolin as an internal standard. For the analysis of plasma samples two calibration curves were utilized covering the cefonicid concentration ranges of 0.05-1.0 microgram/ml and 1.0-50.0 micrograms/ml, respectively. Coefficients of variation of 7.4% or less were obtained for cefonicid concentrations of 0.05-50.0 micrograms/ml. Mean bias was +6.0% at 0.05 micrograms/ml cefonicid and between -2.1% and +1.6% for 1.0-50.0 micrograms/ml cefonicid. Plasma samples containing 30 ng/ml cefonicid could be well distinguished from blank plasma samples. Urine samples were analysed by using a calibration curve for cefonicid concentrations between 1.0 and 50.0 micrograms/ml. ranged from 8.6% at a cefonicid concentration of 1.0 microgram/ml to 0.5% at 50.0 micrograms/ml with a mean bias between -3.0% and +0.3%.

Cefamandole↗

PubMedDate not supplied

Cefonicid: an overview of clinical studies in the United States.

Cefonicid, an investigational cephalosporin with a half-life just under 5 hr, was studied by more than 100 investigators in the United States. Of 1,060 cefonicid-treated patients for whom the clinical efficacy of the compound could be evaluated, 91.7% were cured or improved; 95% received a single daily dose. Rates of bacteriologic cure were equal for infections due to gram-positive cocci (89.9%) and gram-negative bacilli (93.2%). Overall rates of favorable response to cefonicid therapy, by disease, were 88.4%, urinary tract infections; 91.4%, lower respiratory tract infections; 95.1%, skin and skin-structure infections; and 91.3%, bone and joint infections. Prophylaxis with cefonicid administered 1 hr before surgery was as effective as that with control antibiotic in reducing the incidence of perioperative infection. For 795 patients who received cefonicid or control drug who underwent gynecologic surgery, prosthetic arthroplasty, cesarean section, or intraabdominal surgery, the reduction in incidence of perioperative infections were equivalent. Resistance to cefonicid developed infrequently (1.3%). Overall safety of cefonicid was comparable with that of control agents except for the frequency of occurrence of diarrhea, which was lower among patients who received cefonicid than among those who received a control drug.

Bacterial Infections↗

PubMedDate not supplied

Penetration of cefonicid into human breast milk and various body fluids and tissues.

A new cephalosporin, cefonicid (1 g), was given intramuscularly to 49 patients 1 hr before they were to undergo surgery and to 10 healthy lactating women. The concentration of cefonicid was assayed by disk agar diffusion with the use of Bacillus subtilis as the test organism. Concentrations of cefonicid in tissue and fluid specimens were obtained. The data demonstrate that within 1 hr of intramuscular injection of cefonicid, effective concentrations of cefonicid in serum and tissue for common microbial pathogens were achieved. This finding suggests that cefonicid would be useful for perioperative prophylaxis in surgical patients. Although the concentration of cefonicid in breast milk was low at 1 hr after injection, more information is needed regarding the subsequent secretion of cefonicid before a conclusive statement can be made concerning the danger of sensitization in infants of nursing mothers.

Adult↗

PubMedDate not supplied

Single-dose treatment of uncomplicated gonorrhea: a comparison of cefonicid and penicillin.

Cefonicid, a parenteral semisynthetic cephalosporin, achieves high and sustained serum levels in humans. Activity against strains of Neisseria gonorrhoeae, including those that produce beta-lactamase, has been shown in vitro. The efficacy of 1.0 g of cefonicid was evaluated noncomparatively in 50 men with gonococcal urethritis; four failed to respond to treatment. Additionally, 57 men and 34 women received either 1.0 g of cefonicid or 4.8 X 10(6) units of procaine penicillin G plus 1.0 g of probenecid in a double-blind study. Among 17 men treated with penicillin, two failed to respond, and one failed among the 33 patients treated with cefonicid. Seventeen women received 1.0 g of cefonicid, and all cervical infections were cured. Among those who received cefonicid, 13 had rectal infections; and four had positive cultures at follow-up four to seven days posttreatment. Among the 17 women receiving penicillin, none failed to respond to therapy; only seven had both cervical and rectal infection. Of the 116 pretreatment and seven posttreatment isolates tested, 45 (37%) were inhibited by less than 0.0625 microgram of penicillin/ml and 121 (98%) were inhibited by less than 1.0 microgram/ml. Forty-one (33%) of the 123 isolates were inhibited by less than 0.0625 microgram of cefonicid/ml and 122 (99%) by less than 1.0 microgram of cefonicid/ml. The median MIC of cefonicid for the strains isolated from the women whose rectal infections were cured was 0.125 microgram/ml; that for the strains isolated from the women with rectal infections who failed to respond was 0.5 microgram/ml. Administration of 1.0 g of cefonicid intramuscularly is effective therapy for uncomplicated gonococcal urethritis in men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Disposition of intramuscular cefonicid in elderly patients.

OBJECTIVE: To examine the disposition of intramuscular (IM) cefonicid in elderly patients with bacterial pneumonia. DESIGN: Pharmacokinetic study. SETTING: A 620-bed university-affiliated long-term care institution with its own 39-bed acute care unit. PATIENTS: Nine consecutive elderly patients with bacterial pneumonia treated with IM cefonicid. MEASUREMENTS: Blood samples were collected on the seventh day of therapy over a 24-hour period and analyzed by high performance liquid chromatography. Pharmacokinetics parameters (volume of distribution, half-life, and clearance) and protein binding were calculated. Clinical outcome of IM cefonicid therapy was also noted. RESULTS: The estimated creatinine clearance (CIcr) ranged from 32 to 145 mL/min. Peak cefonicid serum concentrations occurred at 0.5-1.5 hours, with a mean value of 118 +/- 41 micrograms/mL. Cefonicid concentrations declined monoexponentially to 57 +/- 16 micrograms/mL at 12 hours and 28 +/- 14 micrograms/mL at 24 hours. The mean apparent distribution volume was 0.2 +/- 0.07 L/kg, and the mean apparent total clearance was 15 +/- 12 mL/min. The half-life ranged from 3.1 to 38 hours. A linear correlation was noted between Clcr and cefonicid clearance (r = 0.99). CONCLUSIONS: Cefonicid absorption was variable among these patients, and the serum half-life was longer than previous values noted in younger patients with similar degree of renal dysfunction. Pharmacokinetic and clinical outcome data from our study group indicate the potential role of IM cefonicid in treating elderly patients with bacterial pneumonia.

Absorption↗

PubMed1991

Cefonicid versus clindamycin prophylaxis for head and neck surgery in a randomized, double-blind trial, with pharmacokinetic implications.

Perioperative single-dose antibiotic prophylaxis of cefonicid was compared with clindamycin in a prospective, randomized, double-blind trial of patients undergoing oncologic head and neck surgery. Antibiotics were administered intravenously beginning 1 to 2 h preoperatively. Cefonicid, 1 g, was given as a single dose. Clindamycin, 600 mg, was administered every 8 h for a total of four doses. Blood and wound drainage samples were collected for 24 h following the dose of cefonicid and assayed for total and free cefonicid concentrations, using reverse-phase high-performance liquid chromatography. Although total concentrations of cefonicid in both serum and wound drainage exceeded the MIC for 90% of the isolates of common bacterial pathogens for 24 h, free concentrations in serum and wound drainage (11.0 and 14.9% of total concentrations) were subinhibitory within 6 h following administration. Free concentrations of cefonicid in the postoperative wound drainage were subinhibitory for the entire study period, both perioperatively and postoperatively. Postoperative wound infection occurred significantly (P less than 0.05) more frequently in patients receiving cefonicid (24%) as compared with those receiving clindamycin (8.2%). The relatively low free levels of cefonicid achieved in serum and wound drainage were attributed to the high degree of protein binding (89% in serum) and may be related to the poor clinical outcome.

Cefonicid↗

PubMed1992

Influence of angiotensin II-induced alterations in renal flow on excretion of cefonicid in isolated perfused rat kidneys.

The effects of variations in renal perfusate flow on the excretion of cefonicid was examined in isolated perfused rat kidneys. Cefonicid, an expanded-spectrum cephalosporin, is primarily eliminated by active tubular secretion and is neither metabolized nor reabsorbed in the isolated kidney. We used angiotensin II (AII), a strong vasoconstrictor hormone of the afferent and the efferent arterioles in the kidney, to determine whether the renal and secretion clearances, as well as the excretion ratio (ER = CLR/[fu x GFR], where CLR is renal clearance, fu is the unbound fraction, and GFR is glomerular filtration rate), of this low-extraction compound can be altered by a decreased perfusion flow. Control studies were performed in the absence (n = 5) and presence (n = 4) of AII; cefonicid studies were performed in the absence (n = 4) and presence (n = 5) of AII. AII (1 to 4 ng/min) and cefonicid (5 to 10 micrograms/min) were infused into the perfusate. Cefonicid was assayed by high-performance liquid chromatography, and its protein binding was determined by ultrafiltration. AII decreased the perfusate flow rate and increased the renal vascular resistance and filtration fraction of the isolated kidney in the presence and absence of cefonicid. The glomerular filtration rate remained unchanged among the groups. The fractional excretion of glucose was low and steady, indicating a well-preserved tubular function. Although the unbound fraction was unchanged between treatments, the renal and secretion clearances and the excretion ratio of cefonicid were reduced by about 40% in the presence of AII (excretion ratios, 10.3 without AII versus 6.03 with AII). These results suggest that the altered clearance parameters of cefonicid are the result of a flow-induced change in the intrinsic secretory transport of the drug.

Angiotensin II↗

PubMed1990

[Pulmonary and tonsillar distribution of ceftriaxone and cefonicid and the resultant bactericidal activity of the organ].

The therapeutic efficacy of Ceftriaxone and Cefonicid 1 g I.M. single-dose against S. Pneumoniae, H. Influenzae and K. Pneumoniae in tonsil and lung infections was studied using bactericidal quotient (BQ). Samples of lung tissue and serum were obtained from two groups of surgical patients, treated with Ceftriaxone or Cefonicid 1 g I.M., 2-8-16 and 24 hours before surgery. From two other groups of 10 surgical patients, treated as above, samples of tonsil tissue and serum were obtained. In lung tissue the higher levels of Ceftriaxone and Cefonicid appeared at the second hour (11.54 +/- 1.59 mcg/g and 11.4 +/- 2.49 mcg/g respectively); the lower values were observed at the 24th hour (2.18 +/- 0.47 mcg/g for Ceftriaxone and 0.64 +/- 0.21 mcg/g for Cefonicid). Higher Ceftriaxone and Cefonicid levels also appeared in tonsil tissue at the 2nd hour (11.12 +/- 2.42 mcg/g and 9.22 +/- 3.12 mcg/g respectively); the lower values were observed at the 24th hour (1.54 +/- 0.46 mcg/g for Ceftriaxone and 0.42 +/- 0.23 mcg/g for Cefonicid). BQ values were estimated using the ratio between the mean concentrations of Ceftriaxone and Cefonicid in tissue samples and the MBC mean values determined for the above mentioned pathogens, isolated in hospital. Ceftriaxone always showed BQ values greater than 1 during 24 hours versus levels observed for the three reported pathogens. Cefonicid showed BQ values greater than 1 during 24 hours against S. Pneumoniae and BQ values less than 1 for 6-8 hours against H. Influenzae and for 1-4 hours against K. Pneumoniae.

Adolescent↗

PubMed1985

Clinical efficacy of cefonicid in the treatment of staphylococcal infections.

Cefonicid is a parenteral cephalosporin with a half-life of 4.5 hours, which permits once-daily dosing. The efficacy of cefonicid in the treatment of established staphylococcal infections was reviewed in all patients with infections due to staphylococci who were treated with cefonicid during the US clinical development program. Two hundred evaluable cases were identified, of which 95 had other pathogens as well. Cefonicid was clinically effective in 92% of skin and soft tissue infections, 74% of bone and joint infections, 83% of respiratory tract infections, and 95% of urinary tract infections. None of the three evaluable patients with Staphylococcus aureus endocarditis responded to cefonicid. Thus, based on current evidence, cefonicid is not effective in the treatment of established staphylococcal endocarditis. However, for the treatment of staphylococcal infections at other sites, cefonicid is comparable to other cephalosporins, most of which must be administered more frequently than cefonicid and thus are less cost-effective.

Cefamandole↗

PubMedDate not supplied

Treatment of urinary tract infections in hospitalized patients: a double-blind comparison of cefonicid and cefamandole.

In a randomized double-blind comparison of cefonicid (dose, 1.0 g every 24 hr) and cefmandole (dose, 1.0 g iv every 6 hr), 147 hospitalized patients (105 men, 42 women) with urinary tract infections (UTIs) were assessed. Ninety-one of the men had complicated UTIs. For the 62 cefonicid-treated men, 61 of 62 etiologic pathogens were eliminated. For 17 patients, reinfection with the pretherapy pathogen occurred in the five- to nine-day posttherapy follow-up. Overall cure rate for cefonicid in the treatment of complicated UTIs was 71%. For the 29 cefamandole-treated men, 28 of 29 etiologic pathogens were eliminated. Reinfection occurred in nine patients. Overall cure rate for cefamandole in the treatment of complicated UTIs was 66%. All 14 men (nine receiving cefonicid; five, cefamandole) with uncomplicated infection were cured. For 25 cefonicid-treated women, cure rate was 84%; one of the failures was due to persistence of the pathogen; three were reinfections during follow-up. For 17 cefamandole-treated women, the cure rate was 82%; two of the failures were due to persistence of the pathogen, and one was a reinfection. Similar, minimal adverse reactions occurred with both drugs. Cefonicid is as effective as cefamandole in curing complicated UTIs in men and uncomplicated infections in both sexes. Cefonicid, however, offers the advantage of once-daily therapy.

Adult↗

PubMedDate not supplied

Single-dose treatment of uncomplicated gonococcal urethritis: a comparison of cefonicid and penicillin.

Cefonicid, a parenterally administered semisynthetic cephalosporin, produces high and sustained serum levels in humans. It is active in vitro against Neisseria gonorrhoeae, including beta-lactamase-producing strains. Therefore, the efficacy of cefonicid in treatment of men with uncomplicated gonococcal urethritis was evaluated in a two-phase study. Initially, 58 men were treated intramuscularly with 1 g of cefonicid. There were four failures among the 50 patients who could be evaluated. In the second phase (a double-blind study), 57 men received either 1.0 g of cefonicid or 4.8 x 10(6) units of procaine penicillin G plus 1.0 g of probenecid. Among 17 men treated with penicillin, there were two failures; among the 33 cefonicid-treated patients, there was only one failure. Thus, 78 (94%) of 83 patients receiving cefonicid were cured. Of the 85 pretreatment and four posttreatment isolates tested, 31 were inhibited by less than 0.0625 microgram of penicillin/ml and 87 were inhibited by less than 1.0 microgram/ml. Twenty-eight of the 89 isolates were inhibited by less than 0.0625 microgram of cefonicid/ml and 88, by less than 1.0 microgram of cefonicid/ml. It is concluded that 1.0 g of cefonicid given intramuscularly is effective therapy for uncomplicated gonococcal urethritis.

Cefamandole↗

PubMed1983

Single-dose cefonicid therapy for urinary tract infections.

The efficacy of single-dose therapy with cefonicid (1 g intramuscularly) and multidose therapy with amoxicillin (500 mg orally three times a day for 7 days) was compared for the treatment of uncomplicated lower urinary tract infection in women. Of 50 patients with symptoms of lower urinary tract infection randomized to receive either cefonicid or amoxicillin, 39 were infected with greater than or equal to 10(5) bacteria per ml. At early posttherapy follow-up (5 to 18 days), 19 of 21 (90%) cefonicid-treated patients and 16 of 18 (89%) amoxicillin-treated patients were cured. At late posttherapy follow-up (6 to 7 weeks), 16 of 18 (89%) cefonicid-treated patients and 14 of 15 (93%) amoxicillin-treated patients were cured. One patient was lost to follow-up in each late follow-up group. There were fewer side effects in the cefonicid-treated group. There were significantly more organisms resistant to amoxicillin than to cefonicid in the study population. Considering the small size of the series, single-dose therapy with cefonicid for lower urinary tract infection in women appears to be as safe and effective as conventional multidose therapy with amoxicillin.

Adult↗

PubMed1986

Effect of saturable serum protein binding on the pharmacokinetics of unbound cefonicid in humans.

Previous studies have demonstrated high, concentration-dependent serum protein binding of cefonicid. To determine the in vivo pharmacokinetic significance of these observations, the pharmacokinetics of both total and unbound (non-protein-bound) cefonicid was studied in six volunteers after a single intravenous dose of 30 mg/kg. Saturable serum protein binding was observed in vivo; the mean +/- standard deviation free fraction of cefonicid was 17.6 +/- 6.1% immediately after administration and declined to a constant value of approximately 2% as total serum concentrations fell below 100 micrograms/ml. This nonlinear binding was associated with a pronounced decline in unbound serum cefonicid concentrations during the first 3 h after administration, with low or undetectable unbound drug concentrations by 12 h. Renal clearance of total cefonicid averaged 21.1 ml/min per kg and did not vary with time; in contrast, the mean +/- standard deviation unbound cefonicid renal clearance increased from 5.7 +/- 2.1 to 10.8 +/- 1.6 ml/min per kg with time (P less than 0.02). This study may partially explain the poor results obtained with single daily dosing of cefonicid in endocarditis. Dosage regimens of certain antimicrobial agents with high, saturable serum protein binding and extensive renal tubular secretion may be most appropriately designed based on unbound drug pharmacokinetics.

Adult↗

PubMed1983

Evaluation of the cefonicid disk test criteria, including disk quality control guidelines.

Cefonicid (SKF 75073) is a second-generation cephalosporin which has a spectrum of antimicrobial activity similar to that of cefamandole, but cefoxitin (a cephamycin) and cephalothin have uniquely different spectra of activity. The second-generation cephalosporins tested displayed comparable susceptibility to beta-lactamases and inhibited type I beta-lactamases. Although cefonicid has a longer serum half-life (3 to 4 h) compared with the currently used drugs, the same minimal inhibitory concentration breakpoints separating susceptible and resistant categories were applied to tests with cefonicid, cefamandole, and cephalothin. Regression analysis of the disk diffusion test results confirmed the use of identical zone size breakpoints for 30-micrograms cefonicid, cefamandole, and cephalothin disks: all three produced similar parabolic regression lines. Further analysis of disk test data confirmed the fact that cefonicid and cefamandole disks might be used interchangeably. But for routine tests, cefonicid disks might be preferred in order to minimize the number of very major (false-susceptible) interpretive errors. Suggested cefonicid 30-micrograms disk interpretive criteria are: susceptible, greater than or equal to 18 mm (less than or equal to 8.0 micrograms/ml), and resistant, less than or equal to 14 mm (greater than 16 micrograms/ml). Quality control zone diameter limits were calculated from data obtained in a multilaboratory collaborative study.

Bacteria↗

PubMedDate not supplied

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

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.

Adult↗