7177-50-6

Unipen,Wyeth,US,1964

Antibacterial;Bacterial transpeptidase inhibitor

Nafcillin sodium salt monohydrate is an antibiotic resistant to beta-lactamase.

ChEBI: Nafcillin sodium monohydrate is an organic sodium salt and a hydrate. It contains a nafcillin sodium.

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.

Nallpen (GlaxoSmithKline).

Antibacterial

Nafcillin sodium, 6-(2-ethoxy-1-naphthyl)penicillin sodium(Unipen), is another semisynthetic penicillin that resultedfrom the search for penicillinase-resistant compounds. Likemethicillin, nafcillin has substituents in positions ortho tothe point of attachment of the aromatic ring to the carboxamidegroup of penicillin. No doubt, the ethoxy group andthe second ring of the naphthalene group play steric roles instabilizing nafcillin against penicillinase. Very similar structureshave been reported to produce similar results in somesubstituted 2-biphenylpenicillins.
Unlike methicillin, nafcillin is stable enough in acid topermit its use by oral administration. When it is givenorally, its absorption is somewhat slow and incomplete,but satisfactory plasma levels may be achieved in about1 hour. Relatively small amounts are excreted throughthe kidneys; most is excreted in the bile. Even thoughsome cyclic reabsorption from the gut may occur, nafcillingiven orally should be readministered every 4 to 6 hours.This salt is readily soluble in water and may be administeredintramuscularly or intravenously to obtain highplasma concentrations quickly for the treatment of seriousinfections.
Nafcillin sodium may be used in infections causedsolely by penicillin G-resistant staphylococci or whenstreptococci are present also. Although it is recommendedthat it be used exclusively for such resistant infections, nafcillin is also effective against pneumococci and groupA -hemolytic streptococci. Because, like other penicillins,it may cause allergic side effects, it should be administeredwith care.