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Cloxacillin

Cloxacillin is a penicillinase resistant semisynthetic penicillin. The chemical formula of this is 3-o-chlorophenyl-5-methyl-4-isoxazolyl penicillin [1]; it differs from oxacillin only by an additional chlorine atom.

Therapeutic use

Used to treat infections caused by penicillinase-producing staphylococci, including pneumococci, group A beta-hemolytic streptococci, and penicillin G-sensitive and penicillin G-resistant staphylococci.

Dosage and Administration

Cloxacillin is available  as oral capsules of 250 and 500 mg, and in an injectable formulation of 250 mg, 500 mg, and 2 g. It is also available as an oral solution of 120 mg/5 ml.

Toxicology

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.

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
child TDLo oral 5600mg/kg/5W- (5600mg/kg)   Israel Journal of Medical Sciences. Vol. 27, Pg. 159, 1991.
 
child TDLo oral 5600mg/kg/5W- (5600mg/kg) KIDNEY, URETER, AND BLADDER: INTERSTITIAL NEPHRITIS Israel Journal of Medical Sciences. Vol. 27, Pg. 159, 1991.
 
man TDLo oral 429mg/kg/10D- (429mg/kg) BLOOD: EOSINOPHILIA

KIDNEY, URETER, AND BLADDER: INTERSTITIAL NEPHRITIS

KIDNEY, URETER, AND BLADDER: "CHANGES IN TUBULES (INCLUDING ACUTE RENAL FAILURE, ACUTE TUBULAR NECROSIS)"
Annals of Pharmacotherpy. Vol. 26, Pg. 1241, 1992.
 
mouse LD50 intracrebral 8.1mg/kg   Chemotherapy Vol. 17, Pg. 1111, 1969.
women TDLo intravenous 1680mg/kg/14D (1680mg/kg) LIVER: "JAUNDICE, CHOLESTATIC"

LIVER: LIVER FUNCTION TESTS IMPAIRED

SKIN AND APPENDAGES (SKIN): "DERMATITIS, OTHER: AFTER SYSTEMIC EXPOSURE"
Postgraduate Medical Journal. Vol. 74, Pg. 59, 1998.
women TDLo oral 200mg/kg/5D-I (200mg/kg) LIVER: "JAUNDICE, OTHER OR UNCLASSIFIED"

LIVER: LIVER FUNCTION TESTS IMPAIRED
American Journal of Gastroenterology. Vol. 81, Pg. 1082, 1986

 

Pharmacokinetic

 

Bioavailability 37 to 90%
Protein binding 95%
Metabolism  
Half-life 30 minutes to 1 hour
Cmax (mg/ml)  
tmax (hrs)  
Distribution volume Vd  
Clearance  
Excretion Renal and biliary

Absorption

Well absorbed from the gastrointestinal tract.

Distribution

 

Excretion

 

Metabolism

 

Mechanism of Action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, cloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cloxacillin interferes with an autolysin inhibitor.

Other pharmacological effects

 


Medicinal Chemistry

CAS number: 61-72-3   EINECS: 200-514-7

Molecular Formula:  C19H18ClN3O5S

Average mass: 435.8862 Da

Monoisotopic mass:  435.065582 Da

Systematic name: (2S,5R,6R)-6-{[3-(2-chlorophenyl)-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)c2ccccc2Cl)C(=O)N[C@H]3[C@@H]4N(C3=O)[C@H](C(S4)(C)C)C(=O)O

Std. InChI: 1S/C19H18ClN3O5S/c1-8-11(12(22-28-8)9-6-4-5-7-10(9)20)15(24)21-13-16(25)23-14(18(26)27)19(2,3)29-17(13)23/h4-7,13-14,17H,1-3H3,(H,21,24)(H,26,27)/t13-,14+,17-/m1/s1

ACD/LogP: 2.530.34 # of Rule of 5 Violations: 0
ACD/LogD (pH 5.5): -0.52 ACD/LogD (pH 7.4): -1.20
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 2
Index of Refraction: 1.685 Molar Refractivity: 106.20.4 cm3
Molar Volume: 279.35.0 cm3 Polarizability: 42.10.5 10-24cm3
Surface Tension: 79.25.0 dyne/cm Density: 1.60.1 g/cm3
Flash Point: 370.931.5 C Enthalpy of Vaporization: 106.23.0 kJ/mol
Boiling Point: 689.755.0 C at 760 mmHg Vapour Pressure: 0.02.3 mmHg at 25C

Major Impurities:

Appearance:

Melting point:

Optical rotation:

Solubility:  13.9 mg/L (water)

logP: 2.48

pKa: 2.78

Stability:

 


1. Knudsen E.T., Brown D.M., Rolinson G.N. "A new orally effective penicillinase-stable penicillin BRL. 1621". Lancet 2: 632, (1962).

 

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