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Dicloxacillin

Dicloxacillin is a narrow-spectrum b-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria. It is active against b-lactamase-producing organisms such as Staphylococcus aureus[1], which would otherwise be resistant to most penicillins. It is very similar to flucloxacillin and these two agents are considered interchangeable.

Therapeutic use

Dicloxacillin is more acid-stable than many other penicillins and can be given orally, in addition to parenteral routes. However, like methicillin, it is less potent than benzylpenicillin against non-β-lactamase-producing Gram-positive bacteria.

Dicloxacillin has similar pharmacokinetics, antibacterial activity, and indications to flucloxacillin, and the two agents are considered interchangeable. It is believed to have lower incidence of severe hepatic adverse effects than flucloxacillin, but a higher incidence of renal adverse effects.

Dosage and Administration

Dicloxacillin is commercially available as the sodium salt dicloxacillin sodium in capsules (250 or 500 mg) and injections (powder for reconstitution, 500 and 1000 mg per vial).

Precautions/contraindications

Dicloxacillin is contraindicated in those with a previous history of allergy to penicillins, cephalosporins or carbapenems. It should also not be used in the eye, or those with a history of cholestatic hepatitis associated with the use of dicloxacillin or flucloxacillin.

It should be used with caution in the elderly; patients with renal impairment, where a reduced dose is required; and those with hepatic impairment, due to the risk of cholestatic hepatitis.

Toxicology

 

Pharmacokinetic

 

Bioavailability 60-80%
Protein binding 98%
Metabolism hepatic
Half-life 0.7hrs
Cmax (mg/ml)  
tmax (hrs)  
Distribution volume Vd  
Clearance  
Excretion renal and biliary

Absorption

 

Distribution


Excretion

 

Metabolism

 

Mechanism of Action

Like other β-lactam antibiotics, dicloxacillin acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria.

Other pharmacological effects

 Dicloxacillin is insensitive to beta-lactamase (also known as penicillinase) enzymes secreted by many penicillin-resistant bacteria. The presence of the isoxazolyl group on the side-chain of the penicillin nucleus facilitates the β-lactamase resistance, since they are relatively intolerant of side-chain steric hindrance. Thus, it is able to bind to penicillin-binding proteins (PBPs) and inhibit peptidoglycan crosslinking, but is not bound by or inactivated by β-lactamases.


Medicinal Chemistry

CAS number: 3116-76-5  EINECS:  221-488-3

Molecular Formula:  C19H17Cl2N3O5S 

Average mass: 470.326385 Da

Monoisotopic mass:  469.026581 Da

Systematic name: (2S,5R,6R)-6-{[3-(2,6-dichlorophenyl)-5-methyl-oxazole-4-carbonyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

SMILES: Cc1c(c(no1)c2c(cccc2Cl)Cl)C(=O)N[C@H]3[C@@H]4N(C3=O)[C@H](C(S4)(C)C)C(=O)O

Std. InChI: 1S/C19H17Cl2N3O5S/c1-7-10(12(23-29-7)11-8(20)5-4-6-9(11)21)15(25)22-13-16(26)24-14(18(27)28)19(2,3)30-17(13)24/h4-6,13-14,17H,1-3H3,(H,22,25)(H,27,28)/t13-,14+,17-/m1/s1

ACD/LogP: 3.02±0.39 # of Rule of 5 Violations: 0
ACD/LogD (pH 5.5): -0.03 ACD/LogD (pH 7.4): -0.71
ACD/BCF (pH 5.5): 1.00 ACD/BCF (pH 7.4): 1.00
ACD/KOC (pH 5.5): 1.00 ACD/KOC (pH 7.4): 1.00
#H bond acceptors: 8 #H bond donors: 2
#Freely Rotating Bonds: 4 Polar Surface Area: 138.04 Å2
Index of Refraction: 1.691 Molar Refractivity: 111.0±0.4 cm3
Molar Volume: 290.1±5.0 cm3 Polarizability: 44.0±0.5 10-24cm3
Surface Tension: 81.0±5.0 dyne/cm Density: 1.6±0.1 g/cm3
Flash Point: 372.5±31.5 °C Enthalpy of Vaporization: 106.5±3.0 kJ/mol
Boiling Point: 692.4±55.0 °C at 760 mmHg Vapour Pressure: 0.0±2.3 mmHg at 25°C

 

Major Impurities:

Appearance:

Melting point:

Optical rotation:

Solubility:

logP: 2.91

pKa:

Stability:

 


1. Miranda-Novales G., Leaños-Miranda B.E., Vilchis-Pérez M., Solórzano-Santos F. "In vitro activity effects of combinations of cephalothin, dicloxacillin, imipenem, vancomycin and amikacin against methicillin-resistant Staphylococcus spp. strains". Ann. Clin. Microbiol. Antimicrob. 5: 25, (2006).

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