Nadifloxacin

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Nadifloxacin
Nadifloxacin-2D-skeletal.png
Systematic (IUPAC) name
(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
Clinical data
AHFS/Drugs.com International Drug Names
Legal status
?
Routes topical (epicutaneous)
Identifiers
CAS number 124858-35-1 YesY
ATC code None
PubChem CID 4410
ChemSpider 4257
UNII 6CL9Y5YZEQ YesY
Chemical data
Formula C19H21FN2O4 
Mol. mass 360.379 g/mol
 YesY (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.

Pharmacology[edit]

Antibacterial spectrum[edit]

In vitro studies of nadifloxacin showed potent and broad-spectrum antibacterial activity against aerobic Gram-positive, Gram-negative and anaerobic bacteria, including Propionibacterium acnes and Staphylococcus epidermidis. Nadifloxacin showed 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 quinolones.

Mechanism of action[edit]

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[edit]

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[edit]

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] Despite this it should be noted that 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[edit]

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]

See also[edit]

References[edit]

  1. ^ Murata K, Tokura Y (March 2007). "[Anti-microbial therapies for acne vulgaris: anti-inflammatory actions of anti-microbial drugs and their effectiveness]". J. UOEH (in Japanese) 29 (1): 63–71. 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". J. Dermatol. Sci. 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". Int. J. Dermatol. 50 (3): 350–7. doi:10.1111/j.1365-4632.2010.04701.x. PMID 21342170. 
  4. ^ Murata K, Tokura Y (March 2007). "[Anti-microbial therapies for acne vulgaris: anti-inflammatory actions of anti-microbial drugs and their effectiveness]". J. UOEH (in Japanese) 29 (1): 63–71. 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". Eur J Dermatol 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". J. Dermatol. 40 (8): 620–5. doi:10.1111/1346-8138.12189. PMID 23724808. 
  7. ^ Steinhilber; Schubert-Zsilavecz, Roth (2004). Medizinische Chemie: Targets und Arzneistoffe. WVG Stuttgart. 
  8. ^ Narayanan V, Motlekar S, Kadhe G, Bhagat S (September 2014). "Efficacy and Safety of Nadifloxacin for Bacterial Skin Infections: Results from Clinical and Post-Marketing Studies". Dermatol Ther (Heidelb). doi:10.1007/s13555-014-0062-1. PMID 25212256.