Cloxabiotic Mechanism of Action

Pharmacology: Pharmacodynamics: Cloxacillin is a bactericidal antibiotic that is particularly useful against penicillin-producing staphylococci. Cloxacillin is a semi-synthetic member of the penicillin family. The penicillin nucleus consists of a thiazolidine ring fused with a β-Lactam ring, to which is attached a side-chain. The side-chain determines most of the antibacterial properties of the penicillin in question. It kills bacteria by interfering in the synthesis of the bacterial cell wall. Cloxacillin binds to a penicillin-binding protein (PBPs) on the bacterial cell wall, thus interfering with peptidoglycan synthesis. Peptidoglycan is a heteropolymeric structure that provides the cell wall its mechanical stability. The final stage of peptidoglycan synthesis involves the completion of the cross-linking, where the terminal glycine residue of the pentaglycine bridge is linked to the fourth residue of the pentapeptide (d-alanine). The transpeptidase enzyme that performs this step is inhibited by penicillins and cephalosporins. As a result, the bacterial cell wall is weakened, the cell swells, and then ruptures. Cloxacillin resists the action of bacterial penicillinase probably because of the steric hindrance induced by the acyl side-chain which prevents the opening of the B-lactam ring.
Pharmacokinetics: Blood levels and tissue distribution, peak serum concentration of Cloxacillin are achieved approximately ½-1 hour after intramuscular administration. Peak serum concentrations were 6-7 and 14.7 mg/l after a 250 mg and 500 mg dose respectively.
High serum levels of the drug are achieved when Cloxacillin is administered by intravenous bolus or by short intravenous infusion modes. After an infusion of 2 gm, Cloxacillin in 20 mg/l, 7.5 min, 60 min, and 4 hours, respectively, after the end of the infusion.
The degree of serum protein binding for Cloxacillin has been estimated as 94%. Therefore, through the mean free concentration of Cloxacillin, the serum level of the drug was 14 mg/l. After 2 hours the serum level has fallen 2.3 mg/l.
Toxicology: The toxicology has been investigated in mice, rabbits, rats, and dogs. These animal studies have failed to demonstrate any significant toxic effects of Cloxacillin. Except following subconjunctival injection. Administration of concentrated solutions of the drug to rabbits by this route resulted in the development of an opacity of the cornea which persisted for at least 14 days. Cloxacillin is, therefore, contraindicated for ocular administration. In acute toxicity tests, the LD value in mice for the oral, subcutaneous, and intravenous routes were >5.0, 3.0, and 1.2 gm/kg respectively. There is no evidence that Cloxacillin is teratogenic in mice and rabbits.