Pharmacokinetics of cefonicid in lactating goats after intravenous, intramuscular and subcutaneous administration, and after a long-acting formulation for subcutaneous administration.

The single-dose disposition kinetics of cefonicid were determined in clinically normal lactating goats (n = 6) after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration of a conventional formulation, and after subcutaneous administration of a long-acting formulation (SC-LA). Cefonicid concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time data were analysed by noncompartmental pharmacokinetic methods. Steady-state volume of distribution (Vss ) and clearance (Cl) of cefonicid after IV administration were 0.14 ± 0.03 L/kg and 0.51 ± 0.07 L/h·kg, respectively. Following IM, SC and SC-LA administration, cefonicid achieved maximum plasma concentrations of 14.46 ± 0.82, 11.98 ± 1.92 and 17.17 ± 2.45 mg/L at 0.26 ± 0.13, 0.42 ± 0.13 and 0.83 ± 0.20 hr, respectively. The absolute bioavailabilities after IM, SC and SC-LA routes were 75.34 ± 11.28%, 71.03 ± 19.14% and 102.84 ± 15.155%, respectively. After cefonicid analysis from milk samples, no concentrations were found above LOQ at any sampling time. From these data, cefonicid administered at 20 mg/kg each 12 hr after SC-LA could be effective to treat bacterial infections in lactating animals not affected by mastitis problems.

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.

Penetration of cefonicid into serum, salpinges, cervix and vaginal tissue.

Cefonicid is a new cephalosporin that, given in adequate concentrations is able to kill some pathogens such as Gram-positive cocci and many Enterobacteriaceae. In this study we have evaluated 40 patients receiving 1 g of cefonicid i.m. at various times before abdominal or vaginal hysterectomy. The results of the present study indicate that a single dose of 1 g of cefonicid given intramuscularly is useful as prophylaxis and treatment of gynecological infections.

[Pulmonary and tonsillar distribution of ceftriaxone and cefonicid and the resultant bactericidal activity of the organ]. / Distribuzione polmonare e tonsillare di ceftriaxone e cefonicid e risultante attività battericida d'organo.

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.

In vitro protein binding of cefonicid and cefuroxime in adult and neonatal sera.

The levels of in vitro protein binding of cefonicid and cefuroxime in human adult and neonatal sera were compared. Binding parameters for each drug were determined within the concentration range of 25 to 3,000 micrograms/ml. Cefonicid exhibited concentration-dependent protein binding in both types of sera, with more extensive binding in adult serum at all concentrations. Two classes of binding sites were found: a high-affinity, saturable site and a low-affinity, nonspecific site. Cefuroxime also showed two-class, concentration-dependent protein binding in adult serum, but binding in neonatal serum was to a single class and was independent of drug concentration. Parameters for class 1 binding sites for cefonicid indicated one binding site per albumin molecule in both adult and neonatal sera, with association constants of 7.0 x 10(4) and 1.3 x 10(4) M-1, respectively. These parameters were also derived for cefuroxime in adult serum and were 0.15 and 7.1 x 10(4) M-1, respectively. In neonatal serum, the combined value (number of binding sites per molecule x equilibrium association constant) was similar to combined values calculated for class 2 binding sites for cefuroxime in adult serum and for cefonicid in neonatal serum (287 versus 195 and 261 M-1, respectively). Cephalosporins have been shown to compete with bilirubin for albumin binding sites. Lower levels of protein binding of cefuroxime in the therapeutic range may mean a lower potential for drug displacement of bilirubin in neonates, on the basis of these results. It may be prudent to select less highly protein-bound agents when treating neonatal infections.

Penetration of cefonicid into human lung tissue and lymph nodes.

The present study was undertaken in order to investigate the penetration of cefonicid, a long-acting parenteral cephalosporin, with enhanced activity against most gram-positive and gram-negative pathogens, into human lung tissue and lymph nodes in patients undergoing open thoracotomy. Samples of lung tissue, lymph nodes and serum were obtained at various times after a single intramuscular dose of 1 g. The concentration of cefonicid was assayed by an agar diffusion method with Bacillus subtilis used as the test organism. The mean concentrations of cefonicid in serum at 2, 4, 8, 12 and 24 h after the injection were 91.5, 66.1, 35.7, 21.8 and 2.9 micrograms/ml, respectively. The mean levels of cefonicid into the hilar lymph nodes at the same times were 22.3, 18.7, 12.0, 6.9 and 1.5 micrograms/ml, respectively, while its concentrations in lung tissue were lower than those in lung lymph nodes up to the 12th hour (12.1, 14.6, 7.8, 5.4 and 1.9 micrograms/ml, respectively). Our results show that cefonicid was well distributed in interstitial fluid from which pulmonary lymph is formed and that its concentrations in lung tissue and lymph nodes were sufficient to inhibit most pathogens involved in respiratory tract infections. This finding was considered important, because it demonstrated that the high binding by plasma protein of cefonicid did not prevent it from entering lung tissue and fluids in useful quantities.