Originator
Unipen,Wyeth,US,1964
Uses
As a synthetic beta-lactamase-resistant penicillin, Nafcillin SodiuM Salt can be used to treat infections caused by Gram-positive bacteria, in particular, species of staphylococci that are resistant to other penicillins.
Uses
Nafcillin SodiuM Salt can be used as narcotic antagonist
Definition
ChEBI: Nafcillin sodium is an organic sodium salt. It contains a nafcillin(1-).
Indications
It is effective against Gram-positive cocci and staphylococci that produce penicillinase. It
is used for the same indications as methicillin. Synonyms of this drug are nafcil, nalpen,
unipen, and others.
Another type of semisynthetic penicillin that should undoubtedly be considered is penicillin derivatives of heteroylcarboxylic acids (as a rule an isoxazol) in the third position of
which is present a substituted or nonsubstituted phenyl radical (oxacillin, cloxacillin,
dicloxacillin), which plays the role of the radical in the acyl side group. These penicillins
(oxacillin, cloxacillin, dicloxacillin), which are resistant to penicillinase, are active with
respect to penicillin-G-resistant staphylococci. Their antimicrobial spectrum is restricted
to Gram-positive microorganisms.
Penicillins that are resistant to penicillinase are the drug of choice for infections resistant to penicillin G, Staph. aureus, or coagulase-negative staphylococci. They are also
effective for infections caused by nonenterococcus types of streptococci, such as streptococci groups A, B, C, and G, as well as pneumococci.
Manufacturing Process
A stirred suspension of 12.6 grams 6-aminopenicillanic acid in 130 ml dry
alcohol-free chloroform was treated with 16 ml triethylamine and then with
13.8 grams of a solution of 2-ethoxy-1-naphthoyl chloride in 95 ml
chloroform. After being washed successively with 58 ml each of 1 N and then
0.1 N hydrochloric acid the chloroform solution was extracted with N aqueous
sodium bicarbonate (58 ml + 6 ml). The combined bicarbonate extracts were
washed with 20 ml ether and then evaporated at low temperature and
pressure to give the crude sodium salt of 2-ethoxy-1-naphthylpenicillin [also
called sodium 6-(2-ethoxy-1-naphthamido)penicillinate] as a yellow powder
(20.3 grams). This was dissolved in 20 ml water at 30°C and diluted with 180
ml n-butanol, also at 30°C, with stirring. Slow cooling to 0°C gave colorless
needles of the product.
Brand name
Nallpen (GlaxoSmithKline).
Therapeutic Function
Antibacterial
Antimicrobial activity
The antibacterial spectrum is similar to that of the isoxazolylpenicillins
but it is more active against streptococci
and pneumococci. Activity in vitro is
depressed in the presence of serum. It is more stable than
the isoxazolylpenicillins to staphylococcal β-lactamase.
There is complete cross-resistance with other group 3
penicillins.
Pharmacokinetics
Oral absorption: c. 35%
Cmax 1 g intramuscular:8 mg/L after 1 h
500 mg intravenous:30 mg/L after 5 min
Plasma half-life: 0.5 h
Plasma protein binding: 90%
Absorption and distribution
Nafcillin is poorly absorbed after oral administration, and
absorption is further depressed if the drug is given with
food. Most dosing is now intravenous. Penetration into tissues
is similar to that of the isoxazolylpenicillins. Penetration
into normal meninges is low, but is higher in inflamed
meninges.
Metabolism and excretion
About 60–70% is inactivated in the liver. Following intramuscular
administration, about 30% appears in the urine, producing
concentrations up to 1000 mg/L. Administration of
probenecid reduces the urinary excretion and raises and prolongs
the plasma level. About 8% of the dose is excreted in
the bile.
Clinical Use
Uses are those of group 3 penicillins . Nafcillin has
been particularly recommended for the treatment of staphylococcal
bacteremia caused by susceptible strains.
Side effects
There is cross-allergenicity with other penicillins. Its side
effects are similar to the penicillins. Pseudomembranous colitis
has been reported.
Synthesis
Nafcillin, [2S-(2α,5α,6β)]-3,3-dimethyl-7-oxo-6-(2-ethoxy-1-naphthamido)-4-
thia-1-azabicyclo[3.2.0]-heptan-2-carboxylic acid (32.1.1.4), is synthesized by acylating
6-APA with 2-ethoxy-1-naphthoic acid chloride in the presence of triethylamine.
