Pefloxacin

MECHANISM OF ACTION

Pefloxacin is a fluoroquinolone antibiotic that works by inhibiting bacterial enzymes DNA gyrase (topoisomerase II) and topoisomerase IV. These enzymes are essential for bacterial DNA replication, transcription, repair, and recombination. By blocking their activity, pefloxacin prevents the supercoiling and separation of bacterial DNA strands, which is necessary for cell division. This leads to disruption of DNA synthesis and ultimately results in bacterial cell death, making it a bactericidal agent.

PHARMACOKINETICS

Absorption

Pefloxacin is well absorbed after oral administration, with a bioavailability of approximately 90–100%. It can be taken with or without food, although food may slightly delay absorption. Peak plasma concentrations are typically reached within 1 to 2 hours after ingestion.

Distribution

Pefloxacin is widely distributed throughout body tissues and fluids, including the lungs, liver, kidneys, prostate, and bile. It has a relatively high volume of distribution (about 1.5–2 L/kg) and moderate plasma protein binding (around 20–30%). It penetrates well into intracellular compartments.

Metabolism

Pefloxacin undergoes extensive hepatic metabolism, producing active metabolites such as norfloxacin and pefloxacin N-oxide, which contribute to its antibacterial activity.

Elimination

Pefloxacin is eliminated via both renal and biliary routes. About 60% is excreted in urine (as unchanged drug and metabolites), while the remainder is excreted in feces via bile. The elimination half-life is approximately 8–12 hours, allowing for once or twice daily dosing.

PHARMACODYNAMICS

Pefloxacin is a fluoroquinolone antibiotic that exhibits bactericidal activity by inhibiting DNA gyrase (topoisomerase II) and topoisomerase IV, enzymes essential for bacterial DNA replication and transcription. This inhibition prevents DNA supercoiling and separation, leading to disruption of bacterial cell division and cell death. It is effective against a broad range of Gram-negative and some Gram-positive bacteria.

ADMINISTRATION

Pefloxacin is administered orally or intravenously. Oral tablets are commonly used for outpatient treatment, while IV administration is reserved for severe infections. It should be taken with adequate fluids, and patients are advised to avoid excessive sunlight exposure during treatment.

DOSAGE AND STRENGTH

Typical adult dosage is 400 mg twice daily, depending on the type and severity of infection. Dose adjustments may be required in patients with hepatic impairment.

DRUG INTERACTIONS

Pefloxacin may interact with antacids, iron, zinc, and calcium supplements, which reduce its absorption. It may also enhance the effects of theophylline, caffeine, and anticoagulants. Concurrent use with other drugs that prolong the QT interval should be approached cautiously.

FOOD INTERACTIONS

Pefloxacin can be taken with or without food, but dairy products, antacids, or mineral supplements should be avoided close to dosing as they reduce drug absorption.

CONTRAINDICATIONS

Contraindications include hypersensitivity to fluoroquinolones, pregnancy, breastfeeding, and children/adolescents (due to risk of cartilage damage). It should also be avoided in patients with a history of tendon disorders related to quinolone use.

SIDE EFFECTS

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Headache

• Dizziness 

• Skin rash

• Tendonitis

• Tendon rupture

• Cns effects (confusion, seizures) 

• Photosensitivity.

OVER DOSAGE

Pefloxacin overdose may lead to central nervous system and gastrointestinal toxicity. Common symptoms include nausea, vomiting, abdominal pain, dizziness, headache, restlessness, and confusion. In more severe cases, patients may develop seizures, tremors, or altered mental status due to CNS stimulation.

TOXICITY

Pefloxacin toxicity may result in central nervous system stimulation (restlessness, seizures), gastrointestinal disturbances, and tendon damage. Severe toxicity is uncommon but may occur with overdose or prolonged use. Management is supportive, including discontinuation of the drug and symptomatic treatment.