Nadifloxacin (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

, brand names Acuatim, Nadiflox, Nadoxin, Nadixa, Activon) is a topical

fluoroquinolone A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as wel ...

antibiotic for the treatment of acne vulgaris. It is also used to treat bacterial skin infections.

Pharmacology

Antibacterial spectrum

In vitro studies of nadifloxacin showed potent and broad-spectrum antibacterial activity against aerobic

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...

and

anaerobic bacteria An anaerobic organism or anaerobe is any organism that does not require molecular oxygen for growth. It may react negatively or even die if free oxygen is present. In contrast, an aerobic organism (aerobe) is an organism that requires an oxygenat ...

, including ''

Cutibacterium acnes ''Cutibacterium acnes'' (formerly ''Propionibacterium acnes'') is the relatively slow-growing, typically aerotolerant anaerobic, gram-positive bacterium (rod) linked to the skin condition of acne; it can also cause chronic blepharitis and endopht ...

'' and '' Staphylococcus epidermidis''. Nadifloxacinshowed potent antibacterial activity against methicillin-resistant ''Staphylococcus aureus'' (MRSA), which was similar to potency against methicillin-sensitive ''Staphylococcus aureus'' (MSSA). The drug was also active against new quinolone-resistant MRSA. Nadifloxacin does not show cross-resistance with other new fluoroquinolones.

Mechanism of action

Nadifloxacin inhibits the enzyme

DNA gyrase DNA gyrase, or simply gyrase, is an enzyme within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA-poly ...

that is involved in bacterial DNA synthesis and replication, thus inhibiting the bacterial multiplication. Nadifloxacin in addition to determine a therapeutic antibacterial action, can have a sebostatic and anti-inflammatory action, thus contributing to the improvement of the clinical condition of the patient.

Pharmacokinetics

Following a single topical application of 10 g nadifloxacin 1% cream to normal human back skin, the highest plasma concentration was determined to be 107 ng/mL with an elimination

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...

of 19.4 hours. Approximately 0.09% of the administered dose was excreted in the urine over 48 hours post- dosing. The plasma concentration reached a steady state on Day 5 of repeated administration study when nadifloxacin 1% cream was applied at 5 g twice daily to normal healthy individuals for a period of 7 days. The plasma concentration reached a peak of 4.1 ng/ml at 8 hours post-final dosing with an elimination half-life of 23.2 hours. The urinary excretion rate reached 0.16% on Day 7.

Clinical use

In some European countries, the drug has been approved for the treatment of acne vulgaris. In a 2013 multicenter, randomized clinical study with a total of 184 Japanese patients with moderate to severe acne,

adapalene Adapalene is a third-generation topical retinoid primarily used in the treatment of mild-moderate acne, and is also used off-label to treat keratosis pilaris as well as other skin conditions. Studies have found adapalene is as effective as othe ...

0.1% gel plus nadifloxacin 1% cream (combination therapy) showed a significant efficacy in decrement of inflammatory papulopustular lesions. In patients with skin lesions, topical application of nadifloxacin can result in plasma concentrations of 1 to 3 ng/ml. Consequently, some authors argued that it should not be used to treat relatively harmless diseases like acne vulgaris, risking the development of quinolone resistances.

Adverse effects

During the treatment some patients may develop some adverse effects predominantly of the skin and subcutaneous tissue: burning and

itching Itch (also known as pruritus) is a Wikt:sensation, sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of Sensory system, sensory experience. Itch has many similarities to pain, ...

(in absolute the most common side effect),

contact dermatitis Contact dermatitis is a type of acute or chronic inflammation of the skin caused by exposure to chemical or physical agents. Symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, or swelling. These rashes are ...

, dryness and skin irritation.

References

{{QuinoloneAntiBiotics Flumequines 4-Hydroxypiperidines