Review of nemonoxacin with special focus on clinical development

Abstract

Nemonoxacin is a novel C-8-methoxy nonfluorinated quinolone with remarkably enhanced in vitro activity against a wide variety of clinically relevant pathogens, especially gram-positive bacteria, including multidrug-resistant Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus. It has a low propensity for selecting resistant pathogens than fluoroquinolones, since bacteria become resistant to nemonoxacin only when three different mutations occur in their quinolone resistance-determining regions. Nemonoxacin shows greater efficacy than most of the widely used fluoroquinolones in the murine model of systemic, pulmonary, or ascending urinary tract infection. Nemonoxacin has a sound PK profile in healthy volunteers. It rapidly reaches maximum concentration Cmax 1–2 hours after oral administration in the fasting state and has a relatively long elimination half-life of more than 10 hours, which is similar to fluoroquinolones. Approximately 60%–75% of the administered dose is excreted in unchanged form via kidneys over 24–72 hours. Phase II and III studies of oral nemonoxacin and Phase II studies of intravenous nemonoxacin have been completed in patients with community-acquired pneumonia (CAP), before which the Phase I studies of oral and intravenous nemonoxacin indicated sound tolerance and safety with healthy volunteers. The published results demonstrate that an oral dose of either 500 mg or 750 mg nemonoxacin once daily for 7 days is as effective and safe as levofloxacin 500 mg once daily for 7 days. Nemonoxacin is well-tolerated in patients with CAP. The most common adverse events of oral administration are observed in the gastrointestinal and nervous system, the incidence of which is similar to levofloxacin treatment. The Phase III studies of intravenous nemonoxacin for treating CAP and oral nemonoxacin for diabetic foot infection has been registered with promising outcomes to be expected.

Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

“…Nemonoxacin (trade name Taigexyn), developed by TaiGen Biotechnology Co., Ltd., is a novel non-fluorinated quinolone with potent in vitro activity against Gram-positive bacteria, especially multidrug-resistant S. pneumoniae, MRSA and vancomycin-resistant pathogens [78]. Oral nemonoxacin rapidly reaches maximum concentration one to two hours in the fasting state and has a long half-life of more than 10 h [78]. Approximately 60-75% is excreted via the kidneys over 24 to 72 h [78].…”

“…Oral nemonoxacin rapidly reaches maximum concentration one to two hours in the fasting state and has a long half-life of more than 10 h [78]. Approximately 60-75% is excreted via the kidneys over 24 to 72 h [78]. The addition of a methoxy group at the C-8 position allows nemonoxacin to target both topoisomerase IV and II, resulting in an improved spectrum of activity, whilst the removal of the fluorine residue is thought to reduce the incidence of toxic side effects [79,80].…”

“…The addition of a methoxy group at the C-8 position allows nemonoxacin to target both topoisomerase IV and II, resulting in an improved spectrum of activity, whilst the removal of the fluorine residue is thought to reduce the incidence of toxic side effects [79,80]. Nemonoxacin has a lower propensity for selecting resistant pathogens than fluoroquinolones, as bacteria only become resistant when three different mutations occur in their quinolone resistance-determining regions [78].…”

Pharmacokinetics and Pharmacodynamics of Multiple-Dose Intravenous Nemonoxacin in Healthy Chinese Volunteers

“…Nemonoxacin is generally more active than other fluoroquinolones against Streptococcus pneumoniae strains that are resistant to penicillin (PRSP) or quinolone. The MIC 90 s of nemonoxacin and levofloxacin against PRSP are 0.03 mg/liter and 1 mg/liter, respectively (3)(4)(5)(6)(7)(8)(9)(10). Nemonoxacin is also active against Staphylococcus aureus strains that are resistant to methicillin (MRSA) or vancomycin.…”

“…Nemonoxacin is also active against Staphylococcus aureus strains that are resistant to methicillin (MRSA) or vancomycin. The MIC 90 s of nemonoxacin and levofloxacin against community-acquired MRSA are 0.5 mg/liter and 8 mg/liter, respectively (3)(4)(5)(6)(7)(8)(9)(10).…”