Nadifloxacin

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Nadifloxacin
Nadifloxacin structure.svg
Clinical data
AHFS/Drugs.com International Drug Names
Routes of
administration
topical (epicutaneous)
ATC code
Identifiers
  • (RS)-9-Fluoro-8-(4-hydroxy-piperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard 100.166.530 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H21FN2O4
Molar mass 360.385 g·mol−1
3D model (JSmol)
Chirality Racemic mixture
Melting point 245 to 247 °C (473 to 477 °F) (dec.)
  • CC1CCc2c(N3CCC(O)CC3)c(F)cc3c(=O)c(C(=O)O)cn1c23
  • InChI=1S/C19H21FN2O4/c1-10-2-3-12-16-13(18(24)14(19(25)26)9-22(10)16)8-15(20)17(12)21-6-4-11(23)5-7-21/h8-11,23H,2-7H2,1H3,(H,25,26) X mark.svgN
  • Key:JYJTVFIEFKZWCJ-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Nadifloxacin (INN, brand names Acuatim, Nadiflox, Nadoxin, Nadixa, Activon) is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris. [1] It is also used to treat bacterial skin infections.

Contents

Pharmacology

Antibacterial spectrum

In vitro studies of nadifloxacin showed potent and broad-spectrum antibacterial activity against aerobic Gram-positive, Gram-negative and anaerobic bacteria, including Cutibacterium acnes 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.[ citation needed ]

Mechanism of action

Nadifloxacin inhibits the enzyme DNA gyrase 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. [2] [3] [4]

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 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. [5] In a 2013 multicenter, randomized clinical study with a total of 184 Japanese patients with moderate to severe acne, adapalene 0.1% gel plus nadifloxacin 1% cream (combination therapy) showed a significant efficacy in decrement of inflammatory papulopustular lesions. [6] 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. [7]

Adverse effects

During the treatment some patients may develop some adverse effects predominantly of the skin and subcutaneous tissue: burning and itching (in absolute the most common side effect), contact dermatitis, dryness and skin irritation. [8]

Related Research Articles

<span class="mw-page-title-main">Acne</span> Skin condition characterized by pimples

Acne, also known as acne vulgaris, is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and possible scarring. It primarily affects skin with a relatively high number of oil glands, including the face, upper part of the chest, and back. The resulting appearance can lead to lack of confidence, anxiety, reduced self-esteem, and, in extreme cases, depression or thoughts of suicide.

<span class="mw-page-title-main">Minocycline</span> Antibiotic medication

Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. Minocycline is also used for the treatment of acne and rheumatoid arthritis. It is taken by mouth or applied to the skin.

<span class="mw-page-title-main">Levofloxacin</span> Antibiotic

Levofloxacin, sold under the brand name Levaquin among others, is an antibiotic medication. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. Use is generally recommended only when other options are not available. It is available by mouth, intravenously, and in eye drop form.

<i>Cutibacterium acnes</i> Species of bacterium

Cutibacterium 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 endophthalmitis, the latter particularly following intraocular surgery. Its genome has been sequenced and a study has shown several genes can generate enzymes for degrading skin and proteins that may be immunogenic.

<span class="mw-page-title-main">Tretinoin</span> Medication

Tretinoin, also known as all-trans retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For leukemia, it is taken by mouth for up to three months. Topical tretinoin is also the most extensively investigated retinoid therapy for photoaging.

<span class="mw-page-title-main">Rosacea</span> Skin condition resulting in redness, pimples and swelling, usually on the face

Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarged nose may occur in severe disease, a condition known as rhinophyma.

<span class="mw-page-title-main">Benzoyl peroxide</span> Chemical compound with uses in industry and acne treatment

Benzoyl peroxide is a chemical compound (specifically, an organic peroxide) with structural formula (C6H5−C(=O)O−)2, often abbreviated as (BzO)2. In terms of its structure, the molecule can be described as two benzoyl (C6H5−C(=O)−, Bz) groups connected by a peroxide (−O−O−). It is a white granular solid with a faint odour of benzaldehyde, poorly soluble in water but soluble in acetone, ethanol, and many other organic solvents. Benzoyl peroxide is an oxidizer, which is principally used as in the production of polymers.

<span class="mw-page-title-main">Adapalene</span> Third-generation topical retinoid

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 other retinoids, while causing less irritation. It also has several advantages over other retinoids. The adapalene molecule is more stable compared to tretinoin and tazarotene, which leads to less concern for photodegradation. It is also chemically more stable compared to the other two retinoids, allowing it to be used in combination with benzoyl peroxide. Due to its effects on keratinocyte proliferation and differentiation, adapalene is superior to tretinoin for the treatment of comedonal acne and is often used as a first-line agent. The Swiss company Galderma sells adapalene under the brand-name product Differin.

<span class="mw-page-title-main">Fusidic acid</span> Antibiotic

Fusidic acid, sold under the brand names Fucidin among others, is an antibiotic that is often used topically in creams or ointments and eyedrops but may also be given systemically as tablets or injections.
As of October 2008, the global problem of advancing antimicrobial resistance has led to a renewed interest in its use.

<span class="mw-page-title-main">Ofloxacin</span> Antibiotic to treat bacterial infections

Ofloxacin is a quinolone antibiotic useful for the treatment of a number of bacterial infections. When taken by mouth or injection into a vein, these include pneumonia, cellulitis, urinary tract infections, prostatitis, plague, and certain types of infectious diarrhea. Other uses, along with other medications, include treating multidrug resistant tuberculosis. An eye drop may be used for a superficial bacterial infection of the eye and an ear drop may be used for otitis media when a hole in the ear drum is present.

<i>Staphylococcus epidermidis</i> Species of bacterium

Staphylococcus epidermidis is a Gram-positive bacterium, and one of over 40 species belonging to the genus Staphylococcus. It is part of the normal human microbiota, typically the skin microbiota, and less commonly the mucosal microbiota and also found in marine sponges. It is a facultative anaerobic bacteria. Although S. epidermidis is not usually pathogenic, patients with compromised immune systems are at risk of developing infection. These infections are generally hospital-acquired. S. epidermidis is a particular concern for people with catheters or other surgical implants because it is known to form biofilms that grow on these devices. Being part of the normal skin microbiota, S. epidermidis is a frequent contaminant of specimens sent to the diagnostic laboratory.

<span class="mw-page-title-main">Azelaic acid</span> Organic chemical compound

Azelaic acid (AzA) is an organic compound with the formula HOOC(CH2)7COOH. This saturated dicarboxylic acid exists as a white powder. It is found in wheat, rye, and barley. It is a precursor to diverse industrial products including polymers and plasticizers, as well as being a component of a number of hair and skin conditioners. AzA inhibits tyrosinase.

<span class="mw-page-title-main">Norfloxacin</span> Chemical compound, antibiotic

Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, gonorrhea and bladder infection. Eye drops were approved for use in children older than one year of age.

<span class="mw-page-title-main">Enoxacin</span> Chemical compound

Enoxacin is an oral broad-spectrum fluoroquinolone antibacterial agent used in the treatment of urinary tract infections and gonorrhea. Insomnia is a common adverse effect. It is no longer available in the United States.

<span class="mw-page-title-main">Sparfloxacin</span> Chemical to treat bacterial infections

Sparfloxacin is a fluoroquinolone antibiotic used in the treatment of bacterial infections. It has a controversial safety profile.

<span class="mw-page-title-main">Fleroxacin</span> Chemical compound

Fleroxacin is a quinolone antibiotic. It is sold under the brand names Quinodis and Megalocin.

<span class="mw-page-title-main">Pimple</span> Type of comedo

A pimple or zit is a kind of comedo that results from excess sebum and dead skin cells getting trapped in the pores of the skin. In its aggravated state, it may evolve into a pustule or papule. Pimples can be treated by acne medications, antibiotics, and anti-inflammatories prescribed by a physician, or various over the counter remedies purchased at a pharmacy.

<span class="mw-page-title-main">Adapalene/benzoyl peroxide</span> Pharmaceutical combination

Adapalene/benzoyl peroxide, sold under the brand name Epiduo among others, is a fixed-dose combination medication for the treatment of severe acne vulgaris. It consists of a combination of adapalene and benzoyl peroxide in a topical gel formulation.

Infantile acne is a form of acneiform eruption that occurs in infants from 6 weeks to 1 year of age. Typical symptoms include inflammatory and noninflammatory lesions, papules and pustules most commonly present on the face. No cause of infantile acne has been established but it may be caused by increased sebaceous gland secretions due to elevated androgens, genetics and the fetal adrenal gland causing increased sebum production. Infantile acne can resolve by itself by age 1 or 2. However, treatment options include topical benzyl peroxide, topical retinoids and topical antibiotics in most cases.

<span class="mw-page-title-main">Clascoterone</span> Chemical compound

Clascoterone, sold under the brand name Winlevi, is an antiandrogen medication which is used topically in the treatment of acne. It is also under development in a higher concentration for the treatment of androgen-dependent scalp hair loss, under the brand name Breezula. The medication is used as a cream by application to the skin, for instance the face and scalp.

References

  1. Murata K, Tokura Y (March 2007). "[Anti-microbial therapies for acne vulgaris: anti-inflammatory actions of anti-microbial drugs and their effectiveness]". Journal of UOEH (in Japanese). 29 (1): 63–71. doi:10.7888/juoeh.29.63. PMID   17380730.
  2. Kuwahara K, Kitazawa T, Kitagaki H, Tsukamoto T, Kikuchi M (April 2005). "Nadifloxacin, an antiacne quinolone antimicrobial, inhibits the production of proinflammatory cytokines by human peripheral blood mononuclear cells and normal human keratinocytes". Journal of Dermatological Science. 38 (1): 47–55. doi:10.1016/j.jdermsci.2005.01.002. PMID   15795123.
  3. Jung JY, Kwon HH, Yeom KB, Yoon MY, Suh DH (March 2011). "Clinical and histological evaluation of 1% nadifloxacin cream in the treatment of acne vulgaris in Korean patients". International Journal of Dermatology. 50 (3): 350–357. doi:10.1111/j.1365-4632.2010.04701.x. PMID   21342170. S2CID   22232885.
  4. Murata K, Tokura Y (March 2007). "[Anti-microbial therapies for acne vulgaris: anti-inflammatory actions of anti-microbial drugs and their effectiveness]". Journal of UOEH (in Japanese). 29 (1): 63–71. doi:10.7888/juoeh.29.63. PMID   17380730.
  5. Plewig G, Holland KT, Nenoff P (2006). "Clinical and bacteriological evaluation of nadifloxacin 1% cream in patients with acne vulgaris: a double-blind, phase III comparison study versus erythromycin 2% cream". European Journal of Dermatology. 16 (1): 48–55. PMID   16436342 . Retrieved 2014-09-28.
  6. Takigawa M, Tokura Y, Shimada S, Furukawa F, Noguchi N, Ito T (August 2013). "Clinical and bacteriological evaluation of adapalene 0.1% gel plus nadifloxacin 1% cream versus adapalene 0.1% gel in patients with acne vulgaris". The Journal of Dermatology. 40 (8): 620–625. doi:10.1111/1346-8138.12189. PMID   23724808. S2CID   31595559.
  7. Steinhilber D, Schubert-Zsilavecz M, Roth HJ (2005). Medizinische Chemie: Targets und Arzneistoffe. Deutscher Apotheker Verlag WVG Stuttgart. ISBN   978-3-7692-3483-1.
  8. Narayanan V, Motlekar S, Kadhe G, Bhagat S (December 2014). "Efficacy and safety of nadifloxacin for bacterial skin infections: results from clinical and post-marketing studies". Dermatology and Therapy. 4 (2): 233–248. doi:10.1007/s13555-014-0062-1. PMC   4257952 . PMID   25212256.