Nadifloxacin (INN, brand namesAcuatim,Nadiflox,Nadoxin,Nadixa,Activon) is a topicalfluoroquinoloneantibiotic for the treatment ofacne vulgaris.[1] It is also used to treat bacterial skin infections.
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| AHFS/Drugs.com | International Drug Names |
| Routes of administration | topical (epicutaneous) |
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| ECHA InfoCard | 100.166.530 |
| 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.) |
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Pharmacology
editAntibacterial spectrum
editIn vitro studies of nadifloxacin showed potent and broad-spectrum antibacterial activity against aerobicGram-positive,Gram-negative andanaerobic bacteria, includingCutibacterium acnes andStaphylococcus epidermidis. Nadifloxacinshowed potent antibacterial activity againstmethicillin-resistantStaphylococcus aureus (MRSA), which was similar to potency againstmethicillin-sensitiveStaphylococcus 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
editNadifloxacininhibits the enzymeDNA 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
editFollowing 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 eliminationhalf-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
editIn 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 quinoloneresistances.[7]
Adverse effects
editDuring the treatment some patients may develop some adverse effects predominantly of the skin and subcutaneous tissue: burning anditching (in absolute the most common side effect),contact dermatitis,dryness and skin irritation.[8]
References
edit- ^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.
- ^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.
- ^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.
- ^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.
- ^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. Retrieved2014-09-28.
- ^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.
- ^Steinhilber D, Schubert-Zsilavecz M, Roth HJ (2005).Medizinische Chemie: Targets und Arzneistoffe. Deutscher Apotheker Verlag WVG Stuttgart.ISBN 978-3-7692-3483-1.
- ^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.