Description
Cefdinir is a cephalosporin antibiotic.
1 It is active against numerous Gram-positive and Gram-negative bacteria, including β-lactamase-producing
E. coli,
K. oxytoca,
K. pneumoniae, and
P. aeruginosa clinical isolates (MICs = 0.25-16 μg/ml). Cefdinir is protective against sepsis induced by strains of
S. aureus or
H. influenzae in mice with 50% protective dose (PD
50) values of 2.7-35 and 3.1-5.8 mg/kg, respectively.
2 Formulations containing cefdinir have been used in the treatment of Gram-positive and Gram-negative infections.
Description
Cefdinir is an orally active, beta-lactamase stable cephalosporin with a broad spectrum
of activity. Compared to other oral cephalosporins, cefdinir is more potent against
Gram-positive bacteria, especially Staphylococci. Its activity against Gram-negative
bacteria such as E.coli,K. pneumoniae and P.mirabilis is similar to cefixime, but
superior to cefaclor and cephalexin.
Chemical Properties
Pale Yellow Solid
Originator
Fujisawa (Japan)
Uses
A broad spectrum antibiotic targeting both Gram-positive and Gram-negative pathogens
Uses
A Cephalosporin antibiotic structurally similar to Cefixime
Uses
antihypertensive, ACE inhibitor
Definition
ChEBI: A cephalosporin compound having 7beta-2-(2-amino-thiazol-4-yl)-2-[(Z)-hydroxyimino]-acetylamino- and 3-vinyl side groups.
Manufacturing Process
By interaction of 7-amino-8-oxo-3-vinyl-5-thia-1-azabicyclo(4.2.0)oct-2-ene-
2-carboxylic acid 4-methoxyphenyl ester with 4-bromoacetyl bromide was
prepared 7-(4-bromo-3-oxo-butyrylamino)-8-oxo-3-vinyl-5-thia-1-azabicyclo
(4.2.0)oct-2-ene-2-carboxylic acid 4-methoxyphenyl ester. The active
methylene group in that product was then nitrosated with sodium nitrite. The
initial product spontaneously tautomerizes to afford 7-(4-bromo-2-
hydroxyimino-3-oxo-butyrylamino)-8-oxo-3-vinyl-5-thia-1-azabicyclo(4.2.0)
oct-2-ene-2-carboxylic acid 4-methoxyphenyl ester. By the reaction of that
compound with thiourea and then with trifluoroacetic acid was obtained
(6R,7R)-7-(2-(2-amino-4-thiazolyl)glyoxylamido)-8-oxo-3-vinyl-5-thia-1-
azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid sodium nitrite, (Z)-oxime
(Cefdinir sodium nitrile).
In practice it is usually used as free acid.
Synthesis of 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(trytiloxyimino)acetamido]-3-
vinyl-3-cephem-4-carboxylic acid x p-toluenesulfonic acid x 2 N,N-dimethylacetamide (the precursor of Cefdinir) was described in Patent US
6,093,814.
Therapeutic Function
Antibiotic
Antimicrobial activity
An oral cephalosporin similar in structure to cefixime, but
with a slightly modified side chain at the 7-amino position.
Activity is similar to that of cefixime, but it is more active,
especially against staphylococci. It is not hydrolyzed
by staphylococcal or the common plasmid-mediated
enterobacterial β-lactamases. An enhancing effect on phagocytosis
has been demonstrated in vitro.
Oral absorption is about 35%. A 200 mg oral dose achieves
a plasma concentration of 1 mg/L after c. 3 h. Absorption is
reduced after a fatty meal. Concentrations equal to or higher
than corresponding plasma levels were present in blister fluid
6–12 h after administration of an oral dose. The plasma halflife
is 1.5 h. Protein binding is 60–70%. A total of 12–20%
of the dose was excreted in the urine within 12 h, the renal
elimination declining with increasing dose. The elimination
half-life and peak plasma concentration are increased in renal
failure. About 60% of the drug is removed by hemodialysis.
Side effects and uses are those common to oral
cephalosporins.
Safety Profile
Moderately toxic by ingestion andintravenous routes. Low toxicity by intraperitoneal andsubcutaneous routes. Experimental reproductive effects.When heated to decomposition it emits toxic vapors ofNOx and SOx.
References
[1] De Souza, F.I., Zumiotti, A.V., and Da Silva, C.F. Neuregulins 1-α and 1-β on the regeneration the peripheral nerves[J]. Acta Ortop Bras.
[2] MICHAEL A. COHEN. In vivo therapeutic efficacy of cefdinir (FK482), a new oral cephalosporin, against Staphylococcus aureus and Haemophilus influenzae in mouse infection models[J]. Diagnostic microbiology and infectious disease, 1994, 18 1: Pages 41-47. DOI:
10.1016/0732-8893(94)90132-5
