Source: Υπουργείο Υγείας (CY) Revision Year: 2022 Publisher: MEDOCHEMIE LTD, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus
Pharmacotherapeutic group: Third-generation cephalosporins
ATC code: J01DD12
Cefoperazone is semisynthetic broad-spectrum cephalosporin antibiotic intended exclusively for parenteral administration.
Bactericidal effects of cefoperazone are given by its inhibition of bacterial cell wall synthesis.
Cefoperazone is active in vitro against a number of clinically relevant microorganisms and is resistant to degradation of many beta-lactamases.
The sensitive organisms include:
Gram positive bacteria:
Staphylococcus aureus strains producing and not producing penicillinase
Staphylococcus epidermidis
Streptococcus pneumoniae (formerly Diplococcus pneumoniae)
Streptococcus pyogenes (group A beta-hemolytic streptococci)
Streptococcus agalactiae (group B beta-hemolytic streptococci)
Streptococcus faecalis (enterococci)
Beta-haemolytic streptococci
Gram negative bacteria:
Escherichia coli
Klebsiella species
Enterobacter species
Citrobacter species
Haemophilus influenzae
Proteus mirabilis
Proteus vulgaris
Morganella morgani (formerly Proteus morganii)
Serratia species (including Serratia marcescens)
Salmonella and Shigella
Pseudomonas aerruginosa and some strains of other Pseudomonas
Acinobacter calcoaceticus
Neisseria gonorrhoeae
Neisseria meningitidis
Bordetella pertussis
Yersinia enterocolitica
Anaerobic bacteria:
Gram-positive and Gram-negative cocci (including Peptococcus, Peptostreptoccus and Veillonella species);
Gram-positive bacilli (including Clostridium, Eubacterium and Lactobacillus species); Gram-negative bacilli (including Fusobacterium species, Bacteroides fragilis many strains and other strains of Bacteroides).
After a single dose, cefoperazone reaches high concentrations in serum, bile and urine.
Table 1 shows the serum concentrations of cefoperazone in healthy volunteers after a single 15 minutes intravenous infusion of 1 g, 2 g, 3 g and 4 g and after single intramuscular administration of 1 g and 2 g.
Probenecid does not affect cefoperazone serum concentration.
Table 1. Serum concentrations of cefoperazone:
| Average serum concentrations (μg/ml) | |||||||
|---|---|---|---|---|---|---|---|
| Dose/ route | 0* | 0,5 h | 1 h | 2 h | 4 h | 8 h | 12 h |
| 1 g i.v. | 153 | 114 | 73 | 38 | 16 | 4 | 0.5 |
| 2 g i.v. | 252 | 153 | 114 | 70 | 32 | 8 | 2 |
| 3 g i.v. | 340 | 210 | 142 | 89 | 41 | 9 | 2 |
| 4 g i.v. | 506 | 325 | 251 | 161 | 71 | 19 | 6 |
| 1 g i.m | 32** | 52 | 65 | 57 | 33 | 7 | 1 |
| 2 g i.m. | 40** | 69 | 93 | 97 | 58 | 14 | 4 |
* Hours after administration, time 0 is calculated as moment of completion of the infusion.
** The values found 15 min. after injection.
The mean plasma half-life of cefoperazone is approximately 2 hours, without depending on the method of administration.
Cefoperazone reached therapeutic levels in all tested tissues and body fluids. Levels were tested in the following fluids and tissues: ascites, cerebrospinal fluid (in patients with meningitis), urine, bile and gallbladder wall, sputum and lung tissue, tonsils, nasal cavities, atrium, kidney, ureter, prostate, testes, uterus, fallopian tubes, bone, amniotic fluid and umbilical cord blood.
Cefoperazone is excreted in bile and urine. Maximum concentrations in bile are reached between 1 and 3 hours after drug administration. The concentration in plasma exceeds the hundredfold plasma concentration in the bile.
Reported cefoperazone concentration in bile of patients without biliary obstruction ranges from 66g/ml for 30 minutes to 6000 g/ml for 3 hours following a single intravenous dose of 2 g.
After various doses and routes of administration, the amount of cefoperazone excreted in the urine in subjects with normal renal function during the twelve-hour interval ranges on average between 20-30% of the administered dose. After a 15-minute infusion of 2 g, concentrations over 2200 g/ml were found in the urine. After intramuscular administration of 2 g, approximately 1000 g/ml. concentrations were detected in urine
After repeated administration of Cefoperazone, accumulation of the drug did not occur not in healthy individuals.
In patients with hepatic impairment, prolonged plasma half-life and renal excretion is increased.
In patients with combined renal and hepatic impairment, cefoperazone may accumulate in the serum.
Maximum serum concentration, AUC and half-life are similar in normal subjects and patients with renal impairment.
Cefoperazone had adverse effects on the testes prepubertal rats at all tested doses. Subcutaneous administration of 1000 mg/kg/day (approximately six times the human dose) resulted in decreased weight of the rats, disruption of spermatogenesis; reduced number of germ cells and Sertoli cell vacuolation of the cytoplasm. The severity of these effects was dose-dependent in the range from 100 to 1000 mg/kg/day. Low doses caused a slight decrease in spermatocytes. This effect was not observed in adult rats. Reversible histologically changes were found at all doses except for the high doses. These studies did not evaluate subsequent development of reproductive function in rats. The relevance of these findings to humans is not clear.
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