Cloxacillin

Cloxacillin sodium is an antibiotic belonging to the semi-synthetic penicillin family. Cloxacillin sodium exhibits a bacterial action against sensitive organisms during the active multiplication stage. It acts through the inhibition of biosynthesis of cell wall mucopeptides.

Cloxacillin sodium is bactericidal and has an anti-bacterial spectrum similar to that of benzylpenicillin but is less active. It is also effective in the dosage recommended for treatment of infections caused by streptococci and penicillin-G sensitive staphylococci.

*The average minimal inhibitory concentrations (M.I.C.) of sodium cloxacillin monohydrate for these organisms are as follows:

Sodium cloxacillin monohydrate is rapidly but incompletely absorbed £rom the gastrointestinal tract after oral administration.

When a dose of 500 mg cloxacillin (2 × 250 mg cloxacillin capsules) was administered to fasting adult volunteers a mean peak plasma level of 8.5 µg/mL was obtained with a T_max of 0.88 hr.

A dose of 500 mg cloxacillin reconstituted granules for oral solution yielded peak plasma levels of 13.3 µg/mL with a T_max of 0.58 hr. in fasting adult volunteers.

Oral doses of 250 mg sodium cloxacillin to adult fasting volunteers resulted in 4.8 µg/mL peak serum levels with a T_max of 1 hr.

Mean urinary excretion of cloxacillin after an oral dose of 500 mg was found to be 37%.8 Total urinary excretion in healthy volunteers was 62% of an intravenously injected dose of 750 mg (250 mg/hr for three hours).

Food delays the absorption of cloxacillin sodium cloxacillin. Sodium cloxacillin is bound to serum proteins to the extent of 94%.

The plasma half-life of cloxacillin is reported to be 25 minutes in healthy volunteers following infusion of 750 mg over a 3 hour period. The plasma half-life in uremic patients was increased to 49 minutes.

Cloxacillin passage across the CNS barrier is insufficient for practical purposes unless the meninges are inflamed. Cloxacillin passes the placental barrier as do the penicillins to the extent of about 50% of the mothers plasma level.

Serum concentrations are enhanced if probenecid is given concomitantly.

Acute Toxicity

Cloxacillin sodium shares the lack of toxicity of other penicillins. It has been administered to mice, rats, dogs, cats and rabbits by various routes.

Studies on the acute toxicity of cloxacillin sodium have shown that it has a very low acute toxicity whether given orally or parenterally. Studies on newborn rats also show low toxicity. The oral LD₅₀ in mice was more than 5,000 mg/kg and 1,200 mg/kg by intravenous injection.

Subacute Toxicity

Cloxacillin sodium in doses of 100 mg and 500 mg/kg was administered orally and subcutaneously to two groups of 12 male rats each over a period of 12 weeks. No haematological, biochemical, histological or organ weight abnormalities were observed.

Sodium cloxacillin was administered in doses of 500 mg and 2000 mg/kg twice daily to two groups of 3 dogs each for a period of 4 weeks. No haematological, biochemical or histological abnormalities were noted.

Teratogenicity

No evidence of teratogenicity was reported in a study of sodium cloxacillin given intramuscularly to female rabbits. Six pregnant rabbits were administered 250 mg/kg cloxacillin from the 8th day to the 16th of pregnancy. The animals given cloxacillin had no abortions and delivered normal sized litters with no fetal abnormalities.