OCTIN

Indications

• Bacterial infections of the respiratory tract
• Urinary tract infections
• Skin and soft tissue infections
• Gastrointestinal infections
• Bone and joint infections

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines.

Adults: Refer to the BNF for specific dosing recommendations based on the type and severity of infection.

Mechanism of action

Ofloxacin acts by inhibiting bacterial DNA gyrase and topoisomerase IV, which are essential enzymes for DNA replication and transcription. By binding to these enzymes, ofloxacin prevents the normal supercoiling of DNA, ultimately inhibiting bacterial cell division and growth. This mechanism is particularly effective due to ofloxacin's higher affinity for bacterial enzymes compared to mammalian topoisomerase.

Pharmacodynamics

As a bactericidal agent, ofloxacin disrupts the DNA replication process in bacteria, leading to cell death. It exhibits a concentration-dependent killing effect, meaning that higher drug concentrations can lead to more effective bacterial eradication. The drug's broad-spectrum activity allows it to target a wide range of bacterial pathogens, making it a versatile choice in clinical practice.

Pharmacokinetics

Ofloxacin is well-absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a bioavailability of approximately 98%, and it is widely distributed throughout body tissues and fluids. The drug is primarily eliminated via the kidneys, with a half-life of around 4 to 7 hours. Dosage adjustments may be required in patients with renal impairment to avoid accumulation and potential toxicity.

Contra-indications

• Hypersensitivity to ofloxacin or other quinolones
• Tendinopathy or history of tendon rupture associated with fluoroquinolone use

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• Rash
• Tendon rupture
• QT interval prolongation

Interactions

• Antacids containing magnesium, aluminum, or calcium can reduce the absorption of ofloxacin
• NSAIDs may increase the risk of CNS stimulation
• Warfarin may have enhanced anticoagulant effect when used with ofloxacin

Precautions

• Use with caution in patients with a history of seizures or CNS disorders
• Monitor for signs of tendon damage, especially in elderly patients or those taking corticosteroids
• May cause photosensitivity reactions, advise patients to avoid excessive sunlight

Pregnancy

Ofloxacin should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. It is classified as a category C drug.

Breast-feeding

Ofloxacin is excreted in human breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets
• Injection solution
• Eye drops

Mechanism of action

Ofloxacin acts on DNA gyrase and toposiomerase IV, enzymes which, like human topoisomerase, prevents the excessive supercoiling of DNA during replication or transcription. By inhibiting their function, the drug thereby inhibits normal cell division. Quinolone(s) (QNs) is widely used in infection therapy due to its good antimicrobial characteristics. However, QNs-induced arthropathy of immature animals has led to restrictions on the therapeutic use of these antimicrobial agents. The exact mechanism(s) of QNs-induced chondrotoxicity remain unknown. In the present study, .../the authors/ investigated the possible mechanism of ofloxacin (one typical QNs)-induced injuries of chondrocytes. Juvenile rabbit joint chondrocytes cultured in alginate microspheres were incubated with ofloxacin at concentrations of 0, 2, 5, 10, 20, and 40 microg/mL for up to 96 hr. Concentration of 10 microg/mL ofloxacin induced apoptosis of chondrocyte with visible apoptotic signs, including degradation of poly(ADP-ribose) polymerase, caspase-3 activation, and DNA ladder formation. Furthermore, extracellular signal-regulated kinase 1/2 (phospho-ERK1/2) and growth factor receptor-bound protein 2 (Grb2) were significantly reduced, and similar changes were also observed in the beta(1)-integrin receptor as assessed by immunoblotting. However, the mRNA level of beta(1)-integrin obtained from reverse transcription-polymerase chain reaction remained unchanged. Results of beta(1)-integrin immunoprecipitation have also shown that beta(1)-integrin did not interact with activated intracellular signaling proteins. In addition, ofloxacin did not induce apoptosis and decrease beta(1)-integrin expression in chondrocytes supplemented with Mg(2+), and the ofloxacin-induced apoptosis was caspase-8-dependent, inhibition of which did not affect the expression mode of phospho-ERK1/2 and beta(1)-integrin. Our results demonstrate that ofloxacin affects beta(1)-integrin receptor functions and the ERK mitogen-activated protein kinase signaling pathway, causing caspase-8-dependent apoptosis after exposure of 48 hr. Quinolones are widely used in infection therapy due to their good antimicrobial characteristics. However, there potential joint chondrotoxicity on immature animals has stood in the way of the therapeutic application of these agents, the exact mechanism of which is still unclear. This study was undertaken to investigate the role of oxidative damage in ofloxacin (one typical quinolones)-induced arthropathy. Chondrocytes from juvenile rabbit joints were incubated with ofloxacin at concentrations of 0, 5, 10, 20, 40 and 80 ug/mL, respectively. The extent of oxidative damage was assessed by measuring the reactive oxygen species level, activities of antioxidant enzymes, and oxidative damage to some macromolecules. It was observed that ofloxacin induced a concentration-dependent increase in intracellular reactive oxygen species production, which may be an early mediator of ofloxacin cytotoxicity. Similarly, ofloxacin resulted in a significant lipid peroxidation, revealed by a concentration-dependent increase in the level of thiobarbituric acid reactive substances. At the same time, ofloxacin induced DNA damage in a concentration-dependent manner for 24 hr measured by comet assay, which may be a cause for overproduction of reactive oxygen species. Furthermore, antioxidant enzyme activities, such as glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD), were rapidly decreased after treatment with ofloxacin. In addition, SOD decline and reactive oxygen species production were strongly inhibited, and the loss in cell viability was partly abated by additional glutathione (GSH), N-acetylcysteine (NAC) and dithiothreitol (DTT). In conclusion, these results clearly demonstrated that ofloxacin could induce oxidative stress, lipid peroxidation and DNA oxidative damage to chondrocytes. Ofloxacin is a quinolone antimicrobial agent. The mechanism of action of ofloxacin and o

Pharmacodynamics

Ofloxacin is a quinolone/fluoroquinolone antibiotic. Ofloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Ofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.