Cloxacillin

Absorption

Well absorbed from the gastrointestinal tract.

Toxicity

Oral LD50 in rat and mouse is 5000 mg/kg. Intravenous LD50 in rat is 1660 mg/kg. Symptoms of overdose include wheezing, tightness in the chest, fever, itching, bad cough, blue skin color, fits, and swelling of face, lips, tongue, or throat.

Description

Cloxacillin induced contact dermatitis in a pharmaceutical factory worker with positive reactions to ampicillin but not to penicillin. The chemical formula of this is 3-o-chlorophenyl-5-methyl-4-isoxazolyl penicillin (Knudsen et al., 1962); this differs from oxacillin only by an additional chlorine atom.

Originator

Orbenin,Beecham,UK,1962

The Uses of Cloxacillin

Cloxacillin is a semisynthetic beta-lactamase resistant penicillin antibiotic with antibacterial activity. It is used to treat a wide variety of bacterial infections.

Indications

Cloxacillin is indicated for the treatment of beta-hemolytic streptococcal, pneumococcal, and staphylococcal infections (including beta-lactamase producing organisms).

Background

A semi-synthetic penicillin antibiotic which is a chlorinated derivative of oxacillin.

Definition

ChEBI: Cloxacillin is a semisynthetic penicillin antibiotic carrying a 3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamido group at position 6. It has a role as an antibacterial agent and an antibacterial drug. It is a semisynthetic derivative, a penicillin allergen and a penicillin. It is functionally related to an oxacillin. It is a conjugate acid of a cloxacillin(1-).

Manufacturing Process

The reaction between 6-aminopenicillanic acid (6.5 g) and 3-o-chlorophenyl-5- methylisoxazole4-carbonyl chloride (7.66 g) gave the sodium salt of 3-o-chlorophenyl-5-methyl-4-isoxazolylpenicillin（Cloxacillin） (9.98 g) as a pale yellow solid. Colorimetric assay with hydroxylamine against a benzylpenicillin standard indicated a purity of 68%.The 3-o-chlorophenyl-5-methylisoxazole-4-carboxylic acid, from which the acid chloride was prepared, was obtained by hydrolysis of the ester product of the reaction between o-chlorobenzohydroxamic chloride and ethyl acetoacetate in methanolic sodium methoxide. Reaction with thionyl chloride gave the starting material.

brand name

Allypropymal;Alurate sodium;Aprozal;Isonal;Nervisal;Numal;Somnipron.

Therapeutic Function

Antibacterial

World Health Organization (WHO)

Ampicillin and cloxacillin are listed separately in the WHO Model List of Essential Drugs.

Contact allergens

Cloxacillin is a semisynthetic penicillin close to oxacillin. It induced contact dermatitis in a pharmaceutical factory worker with positive reactions to ampicillin, but not to penicillin. In cutaneous drug reactions such as acute generalized exanthematous pustulosis due to amoxicillin, cross-reactivity is frequent to cloxacillin (personal observations).

Pharmacokinetics

Cloxacillin is a semisynthetic antibiotic in the same class as penicillin. Cloxacillin is for use against staphylococci that produce beta-lactamase.

Side Effects

Common side effects include Upset stomach, nausea, vomiting, diarrhea, gas, and mouth sores may occur.

Metabolism

Cloxacillin, like other penicillins, appears to be metabolized via breakage of the beta-lactam ring to form an inactive penicilloic acid metabolite.

Purification Methods

Purify mandelic acid by Soxhlet extraction with *C6H6 (about 6mL/g) and allow the extract to crystallise. It can also be recrystallised from CHCl3. The S-benzylisothiuronium salt has m 169o (166o) (from H2O). Dry it at room temperature under vacuum. [Beilstein 10 IV 565.]