Nadifloxacin

Nadifloxacin

Clinical data
AHFS/Drugs.com	International Drug Names
Routes of administration	topical (epicutaneous)
ATC code	D10AF05 ( WHO )
Identifiers
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
CAS Number	124858-35-1  Y
PubChem CID	4410
ChemSpider	4257  N
UNII	6CL9Y5YZEQ
CompTox Dashboard (EPA)	DTXSID5046483
ECHA InfoCard	100.166.530
Chemical and physical data
Formula	C19H21FN2O4
Molar mass	360.385 g·mol−1
3D model (JSmol)	Interactive image
Chirality	Racemic mixture
Melting point	245 to 247 °C (473 to 477 °F) (dec.)
SMILES CC1CCc2c(N3CCC(O)CC3)c(F)cc3c(=O)c(C(=O)O)cn1c23
InChI 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
NY  (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

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]

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.