PHARMACOLOGY OF Cefazolin

Pharmacopoeia description

USP 25: A white to slightly off- white, odorless crystalline powder. Slightly soluble in water, in water, in alcohol, and in methyl alcohol; sparing soluble in acetone; practically insoluble in chloroform, in dichloromethane, in ether, and in benzene; soluble in dimethylformamide and in pyridine; very slightly soluble in ethyl acetate, in isopropyl alcohol, and in methyl isobutyl ketone. Store in airtight Container.


Cefazolin Sodium (44-m)

1.05 g of monograph substance is approximately equivalent to 1 g of Cefazolin. Each g of monograph substance represents about 2.1 mmol of sodium.
Cefazolin sodium has been reported to be incompatible with Aminoglycosides and many other Groups. When the pH of a solution exceeds 8.5 there may be hydrolysis and when it is below 4.5 insoluble Cefazolin may be precipitated.

Pharmacopoeial description

Ph. Eur, A white or almost white, very hygroscopic powder. Freely soluble in water; very slightly soluble in alcohol; practically insoluble in ether. A 10% solution in water has a pH of 4.0 to 6.0. Store at a temperature not exceeding 30º in airtight container. Protect from light.

Uses and Administration

Cefazolin is a first –generation cephalosporin Antibiotic used in the treatment of a variety of infection due to susceptible organisms, including billiary-tract infection, Endocarditis (staphylococcal), and peritonitis (associated with continuous ambulatory peritoneal dialysis). It is also used for surgical infection Prophylaxis, including Prophylaxis of these infections, and their treatment, see under Choice of Antibacterial.
Administration and dosage. Corazon is given as the sodium salt by deep intramuscular injection, by slow intravenous injection over 3 to 6 minutes, or by intravenous infusion. Doses are expressed in terms of the equivalent amount of Cefazolin e. The usual adult dose is 0.5 to 1 g every 6 to 12 hours. The usual maximum daily dose is 6 g; although up to 12 g has been used in sever life –threatening infection. Children over 1month may be given 25 to 50 mg per kg body –weight daily in three or four divided doses, increased in severe infection to a maximum of 100 mg per kg daily. For the Prophylaxis of infection during surgery, a 1-g dose is given half to one hour before the operation, followed by 0.5 to 1 g is given every 6 to 8 hours postoperatively for 24 hours, or up to 5 days in creation cases.
Dosage should be reduced in patient with renal impairment and various modification heave been recommend. The manufacturers suggest the following for adults following a loading dose; creatinine clearance 55 mL or more per minute, usual doses; 35 to54 mL per minute, usual doses but at intervals of at least 8 hours; 11 to 34 mL per minute, half the usual dose every 12 hours; 10 mL or less per minute, half the usual dose every 18 to 24 hours.
Other routes of administration used for Cefazolin sodium include intraperitoneal administration in peritoneal dialysis solution and intra –ocular injections. In some countries a modified –release intramuscular formulation of Cefazolin sodium together with the less soluble Dibenzylamine salt of Cefazolin, in the ratio of 1:4 has been used.

Antimicrobial Action

As for Cefalotin Sodium, p.163, although Cefazolin is more sensitive to staphylococcal beta – lactamase. The minimum inhibitory concentrations of Cefazolin for susceptible Gram-positive cocci range from about 0.1 to 1 µg per mL; for the majority of susceptible Gram-negative bacteria concentration of greater then 1µg per mL are required.

Pharmacokinetics

Cefazolin is poorly absorbed from the gastrointestinal tract and is given by intramuscular or intravenous injection. Following a dose of 500 mg given intramuscularly, peak plasma concentration of 30 µg or more per mL are obtained after 1 to 2 hours. About 85% of Cefazolin in the circulation is bound to plasma protein. The plasma half-life of Cefazolin is about 1.8 hours, and is increased in patient with renal impairment. Cefazolin diffuse into ascetic, pleural, and Synovial fluid but not appreciably into the CSF. It cross the placenta into the fetal circulation; only low concentration are detected in breast milk. Cefazolin is excreted unchanged in the urine, mainly by Glomerular filtration with some renal tubular secretion, at least 80% of a dose given intramuscularly being excreted within 24 hours. Peak urine concentration of more then 1 and 4 mg per mL have been reported after intramuscular doses of 0.5 and 1 g respectively. Probenecid delays excretion. Cefazolin is removed to some extent by Haemodialysis.
High billiary concentration has been reported, although the amount execrated by this route is small.