Nadifloxacin

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Nadifloxacin
Nadifloxacin-2D-skeletal.png
Clinical data
AHFS/Drugs.comInternational 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 InfoCard100.166.530 Edit this at Wikidata
Chemical and physical data
FormulaC19H21FN2O4
Molar mass360.385 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
Melting point245 to 247 °C (473 to 477 °F) (dec.)
  • CC1CCC2=C3N1C=C(C(=O)C3=CC(=C2N4CCC(CC4)O)F)C(=O)O
  • 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) ☒N
  • Key:JYJTVFIEFKZWCJ-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  

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[]

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.

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]

References[]

  1. ^ Murata K, Tokura Y (March 2007). "[Anti-microbial therapies for acne vulgaris: anti-inflammatory actions of anti-microbial drugs and their effectiveness]". (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). 4: 233–48. doi:10.1007/s13555-014-0062-1. PMC 4257952. PMID 25212256.
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