LINEZOLID - A ANTIBIOTICS OF OXAZOLIDINONE GROUP

LINEZOLID

 A ANTIBIOTICS OF OXAZOLIDINONE GROUP

Linezolid a antibacterial agent of  a new class of antibiotics, know as Oxazolidinone used for treatment of Gram-positive bacterial infection that are resistant to other antibiotics.

Linezolid is active against most Gram-positive bacteria that cause disease, including Streptococci, Vancomycin-resistant Enterococci(VRI), methicillin-resistant staphylococcus aureus (MRSA), Streptococcus pneumoniae (penicillin-susceptible strains only), Staphylococcus epidermidis(including methicillin-resistant strains), streptocovvus pyogenes, & Enterococcus faecalis. The main uses are infections of the skin and pneumonia.

Mechanism of Action:

Linezolid are a protein synthesis inhibitor that it stops the growth of bacteria by disrupting their production of proteins. Although many antibiotics work this way but linezolid appears to be unique in that it blocks the initiation of protein synthesis and not one of the later steps; therefore, cross-resistance between linezolid and other classes of antibiotics is unlikely.

Pharmacokinetics:

Plasma concentrations of linezolid at steady-state after oral doses of  600 mg given every 12 hours(q12 h).

Absorption :

Linozolid is rapidly and extensively adsorbed after oral dosing. Maximum plasma concentrations are reached approximately 1 to 2 hours after dosing and the absolute bioavailability is approximately 100%. Therefore, linezolid may be given orally or intravenously without dose adjustment. It may be administered without regard to the timing of meals. The time to reach the maximum concentration is delayed from 1.5 to 2.2 hours and Cmax is decreased by about 17% when high fat food is given with linezolid.

Distribution:

Linezolid readily distributes to well-perfuse tissue. The plasma protein binding of it is approximately 31% and is concentration-independent.

Metabolism :

Linezolid in not detectably metabolized by human cytochrome P450 and it does not inhibit the activities of clinically significant human CYP isoforms .

Excretion:

Nonrenal clearance accounts for approximately 65% of the total clearance of linezolid. Under steady-state conditions, approximately 30% of the dose appears in the urin as linezolid, 50% as metabolite. The renal clearance of linezolid is low (average 40 ml/min) and suggests net reabsorption. Virtually no linezolid appears in the feces.

Dosage:

Adult- 600 mg orally every 12 hours.

Geriatric:

The  pharmacokinetics of linezolid are not significantly altered in elderly patients (65 yrs or older). Therefore, dose adjustment for geriatric patients is not necessary.

Pediatric:

Information indicates that pediatric patients dosed with 10mg/kg IV have a similar Cmax but a higher average clearance when corrected by body weight and shorter apparent elimination half-life than adults receiving 625 mg of linezolide. Studies with dose higher than 10mg/kg or more frequent than every 12 hours have not been conducted in pediatric patients.

Gender:

Females have a slightly lower volume of distribution of linezolide than male. Plasma concentrations are higher in female than in males ,which is partly due to body weight difference. After a 600mg dose, mean oral clearance is approximately 38% lower in females than in males. However, there are no significant gender difference in means apparent elimination –rate constant or half-life. Therefore, dose adjustment by gender does not appear to be necessary.

Renal Insufficiency:

Linozolide pharmacokinetics is not altered in patients with any degree of renal insufficiency; no dose adjustment is recommended for patients with renal insufficiency.

Hepatic Insufficiency:

The pharmacokinetics of linezolide in not altered in patients with mild-to-moderate hepatic insufficiency. On the basis of the available information, no dosage adjustment is recommended for patients with mild-to-moderate hepatic insufficiency.

Pregnancy: Teratogenic Effects:

Linezolide was not teratogenic in mice or rate at exposure levels 4-fold (in mice) the expected human exposure level.However, embryo and fetal toxicities were seen there are no adequate and well-controlled studies in pregnant women. Linezolide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus