Pefloxacin

Pefloxacin is an antimicrobial agent. It is a synthetic fluoroquinolone, belonging to the 3rd generation of quinolones.

Mode of Action

 * Chromosomal DNA in bacterial cells occurs mainly in the form of a double stand ring.
 * One of a group of bacterial enzymes- DNA gyrase is responsible for the supercoiling process.
 * Pefloxacin bactericidal affect is due to its ability to inhibit the activity of this vital enzyme.
 * The result of this inhibitions is the prevention of bacterial DNA replication.
 * Although inhibition of DNA replication is undoubtedly the chief means by which Abaktal exerts its antibacterial effect, two other actions are also observed:
 * Pefloxacin reduces the ability of E-coli and staphylococcus to adhere to the walls of uroephithelial cells.
 * Pefloxacin has effects on the immune system, stimulating the phagocytic activity of white blood.

Spectrum of antibacterial activity

 * Extensive in vitro & in vivo testing has established that Abaktal has a broad antibacterial spectrum.
 * The MICs of Pefloxacin even against bacteria resistant to beta-lactams and aminoglycosides are very low
 * Initial plasma level of 4.0 mcg/ml, well above M.I.C. for sensitive pathogens, are ready and rapidly attained after a single 400mg dose (oral or i.v.)
 * Excellent tissue penetration level is achieved with Pefloxacin in human and animals studies
 * Species usually sensitive (MIC < 1pg/ml)are Escherichia coli, Klebsiella, Enterobacter, Serratia, Proteus mirabilis, Protues vulgaris, Citrobacter, Salmonella, Shigella, Haemophilus influenzae, Staphalococcus aureus, and Neisseria gonorrhoea.
 * Species variably sensitive include Streptococcus and Pneumococcus, Pseudomonas aeruginosa, Acinetobacter, Clostridium perfringens, Mycoplasma, and Chlamydia.

Pharmacokinetics

 * After oral administration, Abaktal is well absorbed; the bio availability is 100%.
 * Peak plasma levels is reached in 1-1.5 hours
 * Peak serum levels of 3.8-6.6mcg/ml is attained after single dose of 400mg
 * Peak serum levels after multiple dose of 400mg, 12 hourly is 8-10 mcg/ml
 * Steady state concentration is achieved
 * Dose depended increase in plasma level over the dose of 200- 800mg
 * Food slows the absorption but does not effects bio availability
 * Oral & injectable forms are bio-equivalent
 * Elimination half life is 11-12 hours mainly through metabolites
 * Pefloxacin is metabolized in liver (85%-90%)
 * Plasma protein binding is 20-30%
 * Major route of elimination is renal – 9-16% of the drugs is eliminated unchanged
 * Major metabolites constitute up to 84% of drugs recovered in urine
 * Limited excretion via bile
 * N-dismethyl pefloxacin (norfloxacin) activity unknown
 * Pefloxacin N-oxide active
 * Oxodimethyl activity unknown
 * Oxo pefloxacin activity unknown
 * Pefloxacin achieves high tissue concentration

Tissue				Concentration Bronchial tissues	       5 mcg/ml Oropharyngeal concentration	6 mcg/ml Tonsils	                       9 mcg/ml Maxillary sinus cavity sinus   2.82 mcg/ml, 4.1 mcg/ml, 2-8mcg/ml aspirate sinus cystic fluid nasal secretions Muscles	                       5.6 mcg /ml Gall bladder 	               80 mcg /ml Bile	                       78 mcg /ml Kidney	                       90 mcg /ml Prostate 	               10 mcg /ml Gynecological tissue	       38 mcg/ml 4-6 higher than serum conc., Myometrium-                    38.6 mcg /ml, Fallopian tube                 31.9 mcg /ml, Ovaries                        44.8mcg/ml Pancreatic tissue	       4.6mcg/ml Peritonium	               3.5mcg/ml


 * There are no major change in plasma pharmacokinetics as a function of renal impairment
 * Elimination half life increase slightly to approx.15 hours
 * There is a fall in urinary excretion of Abaktal & its metabolites
 * There is no major change in Abaktal plasma levels whatever the degrees of renal impairment
 * Pefloxacin is not readily dialyzed
 * There are marked changes in pharmacokinetics in patients with hepatic impairment
 * Marked increase in :
 * Elimination half life 3-5 times
 * Area under curve 3-6 times
 * Urinary excretion of unchanged Abaktal 3-4 times
 * Careful monitoring of plasma levels together with appropriate dosage adjustment will be necessary

Indicated for the following conditions:

 * Respiratory infections
 * Ear, nose and throat infections
 * Renal and urinary infections
 * Gynaecological infection
 * Abdominal and hepato-biliary infections
 * Bone and joint infections
 * Skin and soft tissue infection
 * Septicaemia and endocarditis

Contraindications

 * Children or adolescents
 * Pregnant women
 * Nursing mothers
 * History of hypersensitivity to quinolones
 * Patients with a history of tendon lesion tendinitis or tendon rupture

Precautions

 * Hepatic dysfunction
 * Avoid exposure to sunlight during treatment

Side effects

 * Nausea
 * Skin rash
 * Photo sensitivity reaction
 * Insomnia
 * Headache
 * Myalgia
 * Thrombo-cytopenia

Dosage & Presentation
Oral Tablets: 400mg Twice daily

Injection: Administer by slow I.V. at a dosage of 400mg diluted in 100 or 250 ml of 5% isotonic solution (Over a period of 1 hr) Twice daily

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