78439-06-2 Usage
Uses
Used in Antibacterial Applications:
Ceftazidime is used as an antibacterial agent for treating a wide range of gram-negative infections, especially in debilitated patients. It is effective against susceptible strains of organisms causing the following diseases:
1. Lower respiratory tract infections
2. Skin and skin structure infections
3. Urinary tract infections
4. Bacterial septicemia
5. Bone and joint infections
6. Gynecologic infections
7. Intra-abdominal infections (including peritonitis)
8. Central nervous system infections (including meningitis)
Used in Pharmaceutical Industry:
Ceftazidime is used as an active pharmaceutical ingredient in the development of various branded drugs, such as Fortaz (GlaxoSmithKline), Tazicef (Hospira), Tazidime (Lilly), and FORTAM. These brand names are associated with Ceftazidime pentahydrate, which is the hydrate form of the antibiotic, enhancing its therapeutic applications and efficacy in treating the aforementioned infections.
Originator
Glaxo (United Kingdom)
Antimicrobial activity
Its activity is comparable to that of cefotaxime
and ceftizoxime, but it is more active against Ps. aeruginosa,
including almost all gentamicin-resistant strains, and Burk.
cepacia. It is, however, less active against Staph. aureus. It is stable to a wide range of β-lactamases, but is hydrolyzed by
some TEM variants.
Pharmacokinetics
Cmax 500 mg intramuscular: 18–20 mg/L
2 g intravenous (20-min infusion): 185 mg/L end infusion
Plasma half-life: 1.5–2 h
Volume of distribution: 16 L
Plasma protein binding: c. 10%
No accumulation was seen in subjects receiving 2 g every 12
h over 8 days. In premature infants given 25 mg/kg every 12
h, mean peak plasma concentrations were 77 mg/L after intravenous
and 56 mg/L after intramuscular administration, with
plasma elimination half-lives of 7.3 and 14.2 h, respectively.
Postnatal age was the most important determinant of elimination
rate, which was halved after 5 days. In newborn infants
given 50 mg/kg intravenously over 20 min, mean peak plasma
concentrations varied inversely with gestational age from 102
to 124 mg/L, with half-lives of 2.9–6.7 h.
Distribution
The concentration into serous fluids reaches 50% or more of
the simultaneous serum level. In patients given 1 g intravenously
during abdominal surgery, detectable concentrations
appeared within a few minutes in the peritoneal fluid, reaching
a peak around 67 mg/L with a half-life of 0.9 h. Following
a similar intravenous dose, a mean peak of 9.4 mg/L was
reached at 2 h in ascitic fluid. Concentrations in middle ear
fluid after 1 g intravenously were broadly comparable to those
of the plasma.
In patients with meningitis, CSF concentrations of 2–30
mg/L have been found 2–3 h after doses of 2 g intravenously
over 30 min given every 8 h for four doses. Concentrations are
substantially less in the absence of meningitis. Concentrations
of 3–27 mg/g were found in patients with intracranial abscesses
treated with 0.5–2 g every 8 h. Concentrations around 0.4 mg/g
in skin, 0.6 mg/g in muscle and 0.2 mg/g in fatty tissue have
been found in patients given 2 g intravenously over 5 min
preoperatively. A similar dose has produced mean prostate
tissue:serum ratios of around 0.14. Effective concentrations
are achieved in bone: in patients given 1 g intravenously mean
bone concentrations were 14.4 mg/kg 35–40 min after the
dose. There is secretion in breast milk, peak concentrations
being around 5 mg/L at about 1 h in patients receiving 2 g
intravenously every 8 h.
Metabolism and excretion
No metabolites have been detected. Elimination is almost
exclusively renal, predominantly via the glomerular filtrate,
with 80–90% of the dose appearing in the urine in the first 24 h. Elimination half-life is inversely correlated with creatinine
clearance: as the values fall to 2–12 mL/min, the mean
plasma half-life rises to 16 h. In patients maintained on hemodialysis
the half-life fell to 2.8 h on dialysis. No accumulation
occurred over 10 days in severe renal impairment on a daily
dose of 0.5–1 g.
Concentrations of 6.6–58 mg/L have been found in bile
25–160 min after the dose at times when the mean serum
concentration was 77.4 mg/L. In T-tube bile there was considerable
interpatient variation, with mean concentrations of
34 mg/L at 1–2 h after the dose. No accumulation occurs
in patients with impaired hepatic function, but the presence
of ascites, low plasma albumin and accumulation of proteinbinding
inhibitors may increase the volume of distribution.
Clinical Use
It is used, often combined with an aminoglycoside, to treat
a wide range of severe urinary, respiratory and wound infections,
mostly due to enterobacteria or Ps. aeruginosa. Reference
is made to its use in pneumonia, septicemia, meningitis (especially
if caused by Ps. aeruginosa), peritonitis, osteomyelitis,
neonatal sepsis, burns and melioidosis. Concern has been
expressed at the relative frequency with which failure is associated
with superinfection or the emergence of resistance.
Side effects
It is generally well tolerated. Preparations containing arginine
have replaced those with sodium carbonate, which causes
pain on intramuscular injection. Reactions common to cephalosporins
have been observed in some patients, including positive
antiglobulin tests without hemolysis, raised liver function
test values, eosinophilia, rashes, leukopenia, thrombocytopenia
and diarrhea, occasionally associated with toxigenic
C. difficile.
Failure of therapy has been associated with superinfection
with resistant organisms, including Staph. aureus, enterococci
and Candida. Resistance caused by induction of chromosomal
β-lactamases may emerge in Ps. aeruginosa, Ser. marcescens or
Enterobacter spp.
Veterinary Drugs and Treatments
Ceftazidime is potentially useful in treating serious gramnegative
bacterial infections particularly against susceptible
Enterobacteriaceae including Pseudomonas aeruginosa, that are
not susceptible to other, less-expensive agents, or when aminoglycosides
are not indicated (due to their potential toxicity). It is of
particular interest for treating gram-negative infections in reptiles
due to a very long half-life.
Check Digit Verification of cas no
The CAS Registry Mumber 78439-06-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,8,4,3 and 9 respectively; the second part has 2 digits, 0 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 78439-06:
(7*7)+(6*8)+(5*4)+(4*3)+(3*9)+(2*0)+(1*6)=162
162 % 10 = 2
So 78439-06-2 is a valid CAS Registry Number.
InChI:InChI=1/C22H22N6O7S2/c1-22(2,20(33)34)35-26-13(12-10-37-21(23)24-12)16(29)25-14-17(30)28-15(19(31)32)11(9-36-18(14)28)8-27-6-4-3-5-7-27/h3-7,10,14,18H,8-9H2,1-2H3,(H4-,23,24,25,29,31,32,33,34)/b26-13+/t14-,18-/m1/s1
78439-06-2Relevant articles and documents
Process for manufacture of cephalosporin such as ceftazidime and intermediate thereof
-
, (2008/06/13)
This invention relates to reactive derivative of 2-(2-amino-4-thiazolyl)-(Z)-2-?(1-tert butoxycarbonyl-l-methylethoxy) imino!acetic acid of the following formula I STR1 as well as to the use thereof in the manufacture of cephalosporin antibiotic such as ceftazidime of formula II. STR2
Process for the production of cephalosporin derivatives
-
, (2008/06/13)
New process for the production of the pentahydrate of ceftazidime of formula STR1 characterized in that the ester group of the compound of formula STR2 or an acid addition salt thereof, is cleaved by the sole use of aqueous hydrochloric acid, and the resulting ceftazidime is either crystallized directly from the reaction mixture as the pentahydrate by adding a base, or first of all the dihydrochloride of the ceftazidime is isolated by adding acetone and/or ethanol or another anti-solvent which is miscible with water, and this is converted into the pentahydrate by known methods.
Process for recovering ceftazidime
-
, (2008/06/13)
A process for recovering ceftazidime from an aqueous solution containing it, said solution being at a pH in the range 2.0 to 5.5, which comprises contacting the said solution with a non-functional macroreticular resin suitable for adsorbing ceftazidime, eluting the ceftazidime and isolating it, if desired in the form of a salt or hydrate.
(6R,7R)-7-[(Z)-2-(2-Aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-(1-pyridiniummethyl)-ceph-3-em-4-carboxylate and salts thereof
-
, (2008/06/13)
Cephalosporin antibiotics of the general formula STR1 (wherein Ra and Rb, which may be the same or different, each represent a C1-4 alkyl group or Ra and Rb together with the carbon atom to which they are attached form a C3-7 cycloalkylidene group; and R4 represents hydrogen or a 3- or 4-carbamoyl group) exhibit broad spectrum antibiotic activity, the activity being unusually high against gram-negative organisms such as strains of Pseudomonas organisms. A particular antibiotic compound of formula (I) possessing excellent antibacterial activity against strains of Pseudomonas organisms, as well as other valuable therapeutic properties, is (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimono) acetamido]-3-(1-pyridiniummethyl)-ceph-3-em-4 carboxylate. The invention also includes the non-toxic salts and non-toxic metabolically labile esters of compounds of formula (I). Also described are compositions containing the antibiotics of the invention and processes for the preparation of such antibiotics.
