A PROMISING NEW ANTIBIOTIC: MECHANISTIC AND PHARMACOKINETIC OVERVIEW OF GEPOTIDACIN

Gepotidacin, the antibiotic belonging to a brand-new class of triazaacenaphthylene, is being developed for treating infections caused by Gram-negative and some Gram-positive bacteria. This mechanism is different from fluoroquinolones, the drug's targets being bacterial DNA gyrase and topoisomerase IV, which are inhibited simultaneously. Inhibition takes place at a special site that allows the drug to work even when fluoroquinolone binding is ineffective. The drug's pharmacokinetic profile is linear and dose proportional. Besides, the drug has a rapid absorption rate and maximum plasma concentration is reached in 1-2 hours after oral administration. It is also dispersed quite widely in the tissues affected by infections, particularly the genitourinary tract and urinary tract. Gepotidacin is mainly metabolized by hepatic CYP3A4, excreted in both urine and faeces, and has a half-life of 6-12 hours. Compared to the clinical use of the drug, gepotidacin is much safer than traditional fluoroquinolone antibiotics, and the rate of serious adverse effects such as tendon injury, CNS disturbances, and phototoxic reactions is significantly lower. The most common side effects are mild gastrointestinal discomfort and headaches. The drug is so close to its competitors in terms of dual topoisomerase inhibition, unique enzyme binding, and superior pharmacokinetic and safety characteristics that it has turned into a promising candidate for difficult-to-treat bacterial infections.