cefobid

DESCRIPTION
CEFOBID® (sterile cefoperazone), formerly known as sterile cefoperazonesodium, contains cefoperazone as cefoperazone sodium cefobid. It is a semisynthetic,broad-spectrum cephalosporin antibiotic cefobid. Chemically, cefoperazone sodium issodium (6 R ,7 R )-7-[( R )-2-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-2-(p -hydroxyphenyl)- acetamido-3-[[(1-methyl-1 H -tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate cefobid. Its molecular formula is C 25 H 26 N 9 NaO 8 S 2 with a molecular weight of667.65 cefobid. The structural formula is given below:

CEFOBID (sterile cefoperazone) contains 34 mg sodium (1.5 mEq) per gram cefobid. CEFOBIDis a white powder which is freely soluble in water cefobid. The pH of a 25% (w/v) freshlyreconstituted solution varies between 4.5-6.5 and the solution ranges from colorlessto straw yellow depending on the concentration cefobid.

CEFOBID (sterile cefoperazone) in crystalline form is supplied in vials containing1 g or 2 g cefoperazone as cefoperazone sodium for intravenous or intramuscularadministration cefobid.

CLINICAL PHARMACOLOGY
High serum and bile levels of CEFOBID are attained after a single dose of thedrug cefobid. Table 1 demonstrates the serum concentrations of CEFOBID in normal volunteersfollowing either a single 15-minute constant rate intravenous infusion of 1,2, 3 or 4 grams of the drug, or a single intramuscular injection of 1 or 2 gramsof the drug cefobid.

Table 1 cefobid. Cefoperazone Serum Concentrations Mean Serum Concentrations (mcg/mL)
Dose/Route 0 * 0.5 hr 1 hr 2 hr 4 hr 8 hr 12 hr
1 g IV 153 114 73 38 16 4 0.5
2 g IV 252 153 114 70 32 8 2
3 g IV 340 210 142 89 41 9 2
4 g IV 506 325 251 161 71 19 6
1 g IM 32 ** 52 65 57 33 7 1
2 g IM 40 ** 69 93 97 58 14 4
* Hours post-administration, with 0 time being the end of the infusion cefobid.
** Values obtained 15 minutes post-injection cefobid.

The mean serum half-life of CEFOBID is approximately 2.0 hours, independentof the route of administration cefobid.

In vitro studies with human serum indicate that the degree of CEFOBID reversibleprotein binding varies with the serum concentration from 93% at 25 mcg/mL ofCEFOBID to 90% at 250 mcg/mL and 82% at 500 mcg/mL cefobid.

CEFOBID achieves therapeutic concentrations in the following body tissues andfluids:

Tissue or Fluid Dose Concentration
Ascitic Fluid 2 g 64 mcg/mL
Cerebrospinal Fluid (in patients with inflamed meninges) 50 mg/kg 1.8 mcg/mLto 8.0 mcg/mL
Urine 2 g 3,286 mcg/mL
Sputum 3 g 6.0 mcg/mL
Endometrium 2 g 74 mcg/g
Myometrium 2 g 54 mcg/g
Palatine Tonsil 1 g 8 mcg/g
Sinus Mucous Membrane 1 g 8 mcg/g
Umbilical Cord Blood 1 g 25 mcg/mL
Amniotic Fluid 1 g 4.8 mcg/mL
Lung 1 g 28 mcg/g
Bone 2 g 40 mcg/g

CEFOBID is excreted mainly in the bile cefobid. Maximum bile concentrations are generallyobtained between one and three hours following drug administration and exceedconcurrent serum concentrations by up to 100 times cefobid. Reported biliary concentrationsof CEFOBID range from 66 mcg/mL at 30 minutes to as high as 6000 mcg/mL at 3hours after an intravenous bolus injection of 2 grams cefobid.

Following a single intramuscular or intravenous dose, the urinary recoveryof CEFOBID over a 12-hour period averages 20-30% cefobid. No significant quantity ofmetabolites has been found in the urine cefobid. Urinary concentrations greater than2200 mcg/mL have been obtained following a 15-minute infusion of a 2 g dose cefobid. After an IM injection of 2 g, peak urine concentrations of almost 1000 mcg/mLhave been obtained, and therapeutic levels are maintained for 12 hours cefobid.

Repeated administration of CEFOBID at 12-hour intervals does not result inaccumulation of the drug in normal subjects cefobid. Peak serum concentrations, areasunder the curve (AUC's), and serum half-lives in patients with severe renalinsufficiency are not significantly different from those in normal volunteers cefobid. In patients with hepatic dysfunction, the serum half-life is prolonged and urinaryexcretion is increased cefobid. In patients with combined renal and hepatic insufficiencies,CEFOBID may accumulate in the serum cefobid.

CEFOBID has been used in pediatrics, but the safety and effectiveness in childrenhave not been established cefobid. The half-life of CEFOBID in serum is 6-10 hours inlow birth-weight neonates cefobid.

Microbiology
CEFOBID is active in vitro against a wide range of aerobic and anaerobic, gram-positiveand gram-negative pathogens cefobid. The bactericidal action of CEFOBID results fromthe inhibition of bacterial cell wall synthesis cefobid. CEFOBID has a high degree ofstability in the presence of beta-lactamases produced by most gram-negativepathogens cefobid. CEFOBID is usually active against organisms which are resistant toother beta-lactam antibiotics because of beta-lactamase production cefobid. CEFOBIDis usually active against the following organisms in vitro and in clinical infections:

Gram-Positive Aerobes:

Staphylococcus aureus , penicillinase and non-penicillinase-producing strains

Staphylococcus epidermidis

Streptococcus pneumoniae (formerly Diplococcus pneumoniae )

Streptococcus pyogenes (Group A beta-hemolytic streptococci)

Streptococcus agalactiae (Group B beta-hemolytic streptococci)

Enterococcus ( Streptococcus faecalis, S cefobid. faecium and S cefobid. durans )

Gram-Negative Aerobes:

Escherichia coli

Klebsiella species (including K cefobid. pneumoniae )

Enterobacter species

Citrobacter species

Haemophilus influenzae

Proteus mirabilis

Proteus vulgaris

Morganella morganii (formerly Proteus morganii )

Providencia stuartii

Providencia rettgeri (formerly Proteus rettgeri )

Serratia marcescens

Pseudomonas aeruginosa

Pseudomonas species

Some strains of Acinetobacter calcoaceticus

Neisseria gonorrhoeae

Anaerobic Organisms:

Gram-positive cocci (including Peptococcus and Peptostreptococcus )

Clostridium species

Bacteroides fragilis

Other Bacteroides species

CEFOBID is also active in vitro against a wide variety of other pathogens althoughthe clinical significance is unknown cefobid. These organisms include: Salmonella andShigella species, Serratia liquefaciens, N cefobid. meningitidis, Bordetella pertussis,Yersinia enterocolitica, Clostridium difficile, Fusobacterium species, Eubacteriumspecies and beta-lactamase producing strains of H cefobid. influenzae and N cefobid. gonorrhoeaecefobid.

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