Nemonoxacin, a novel nonfluorinated quinolone, exhibits potent in vitro and in vivo activities against community-acquired pneumonia (CAP) pathogens, including multidrug-resistant Streptococcus pneumoniae. Patients with mild to moderate CAP (n ‫؍‬ 265) were randomized to receive oral nemonoxacin (750 mg or 500 mg) or levofloxacin (500 mg) once daily for 7 days. Clinical responses were determined at the test-of-cure visit in intent-to-treat (ITT), clinical per protocol (PPc), evaluable-ITT, and evaluable-PPc populations. The clinical cure rates for 750 mg nemonoxacin, 500 mg nemonoxacin, and levofloxacin were 89.9%, 87.0%, and 91.1%, respectively, in the evaluable-ITT population; 91.7%, 87.7%, and 90.3%, respectively, in the evaluable-PPc population; 82.6%, 75.3%, and 80.0%, respectively, in the ITT population; and 83.5%, 78.0%, and 82.3%, respectively, in the PPc population. Noninferiority to levofloxacin was demonstrated in both the 750-mg and 500-mg nemonoxacin groups for the evaluable-ITT and evaluable-PPc populations, and also in the 750 mg nemonoxacin group for the ITT and PPc populations. Overall bacteriological success rates were high for all treatment groups in the evaluable-bacteriological ITT population (90.2% in the 750 mg nemonoxacin group, 84.8% in the 500 mg nemonoxacin group, and 92.0% in the levofloxacin group). All three treatments were well tolerated, and no drug-related serious adverse events were observed. Overall, oral nemonoxacin (both 750 mg and 500 mg) administered for 7 days resulted in high clinical and bacteriological success rates in CAP patients. Further, good tolerability and excellent activity against common causative pathogens were demonstrated. Nemonoxacin (750 mg and 500 mg) once daily is as effective and safe as levofloxacin (500 mg) once daily for the treatment of CAP.

A method was developed for the quantification of cow milk adulteration in goat milk, based on solvent separation of whey proteins followed by high-performance liquid chromatography with electrospray ionization mass spectrometry (HPLC/ESI-MS). The presence of cow milk was determined using beta-lactoglobulin whey protein as the molecular marker. The adulterants were identified using both retention time and molecular mass derived from multiply charged molecular ions. Standard solutions containing cow and goat milk in different volume ratios were prepared and analyzed. Good linearity covering cow milk content from 5% and above was obtained. The proposed method identifies the adulterants using accurate molecular masses for protein identification and detects the addition of cow milk to goat milk at levels as low as 5%.

Nemonoxacin 500 mg once daily for 7-10 days is as effective and safe as levofloxacin for treating adult CAP patients in terms of clinical cure rates, microbiological success rates, and safety profile. ClinicalTrials.gov identifier: NCT01529476.

Either 500 mg or 750 mg of oral nemonoxacin taken once daily for 7-10 days demonstrated high clinical and bacteriological success rates in Chinese adult patients with CAP. Nemonoxacin at 500 mg once daily for 7-10 days is recommended for future Phase III clinical trials. ClinicalTrials.gov identifier: NCT01537250.

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Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent broad-spectrum activity against Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus, penicillinand quinolone-resistant Streptococcus pneumoniae, and vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus. The safety, tolerability, and pharmacokinetics of nemonoxacin were investigated in a double-blind, ascending-single-dose study involving 56 healthy subjects (48 males and 8 females) who were randomly assigned to 1 of 7 dose cohorts. In each successive cohort, two subjects received a placebo and six received single oral doses of 25, 50, 125, 250, 500, 1,000, or 1,500 mg nemonoxacin. Nemonoxacin was well tolerated up to the maximum dose of 1,500 mg. No severe or serious adverse events were observed. The most frequent adverse events were contact dermatitis, pruritus, and erythema. No clinically significant abnormalities were noted in the electrocardiograms, vital signs, or laboratory tests. The plasma concentrations increased over the dose range, and at 500 mg, the free area under the plasma concentration-time curve/MIC 90 ratios and free maximum nemonoxacin concentration/MIC 90 ratios against drug-sensitive/drug-resistant S. pneumoniae and S. aureus were greater than 227 and 24, respectively. The peak time and elimination half-life of nemonoxacin were 1 to 2 h and 9 to 16 h, respectively. The oral clearance was approximately 0.22 liter/h/kg. The plasma protein binding was approximately 16%. The results of this study support further evaluation of the multiple-dose safety, tolerability, and pharmacokinetics of nemonoxacin.Newer-generation quinolones are largely fluoroquinolones (FQs); they are characterized by the presence of a fluorine at the R6 position of the quinolone nucleus (2, 9, 19). Owing to their improved activity against Gram-positive and atypical pathogens, they have been widely used for the treatment and prophylaxis of bacterial infections. However, the use of FQs has been compromised by the emergence of bacterial resistance (3,8,14,18,22,30) and the potential for adverse side effects (15, 21), including ECG QTc interval prolongation, hepatotoxicity, and phototoxicity. Thus, there is an unmet need for newer compounds that are broad-spectrum agents effective against existing bacterial resistance and that have the potential to minimize the risk of use-limiting adverse effects.Nemonoxacin (TG-873870) (36), a novel nonfluorinated quinolone, has recently been developed from a series of 8-methoxy nonfluorinated quinolones (29) as a malate salt. It differs from FQs in that it lacks the fluorine at the R6 position (Fig. 1); this was formerly believed to be important for the antibacterial potency of FQs. Nemonoxacin has demonstrated broadspectrum activity (4, 20, 28) against Gram-positive, Gramnegative, and atypical pathogens. Furthermore, nemonoxacin appears to be more potent than several FQs, including ciprofloxacin, levofloxacin, and moxifloxacin (20). In preclinical studies, ...

No abstract

Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with broad-spectrum activities againstGram-positive and Gram-negative aerobic, anaerobic, and atypical pathogens, as well as against methicillinresistant Staphylococcus aureus, vancomycin-resistant S. aureus, and multiple-resistant bacterial pathogens. We conducted a randomized, double-blind, placebo-controlled, dose-escalating study to ascertain the safety, tolerability, and pharmacokinetics of nemonoxacin. We enrolled 46 healthy volunteers and used a once-daily oral-dosing range of 75 to 1,000 mg for 10 days. Additionally, the food effect was evaluated in subjects in the 500-mg cohort. Nemonoxacin was generally safe and well tolerated, with no significant changes in the clinical laboratory tests or electrocardiograms. Adverse effects, including headache, contact dermatitis, and rash, were mild and resolved spontaneously. Nemonoxacin was rapidly absorbed within 2 h postdosing, and generally, a steady state was reached after 3 days. The maximum plasma concentration and the area under the plasma concentration-time curve were dose proportional over the dosing range. The elimination half-life was approximately 7.5 h and 19.7 h on days 1 and 10, respectively. Approximately 37 to 58% of the drug was excreted in the urine. Food affected the pharmacokinetics, with decreases in the maximum plasma concentration and area under the plasma concentration-time curve of 46% and 27%, respectively. However, the free AUC/MIC 90 of nemonoxacin was more than 100 under both the fasting and fed conditions, predicting the efficacy of nemonoxacin against most of the tested pathogens. In conclusion, the results support further clinical investigation of once-daily nemonoxacin administration for antibiotic-sensitive and antibiotic-resistant bacterial infections.Nemonoxacin (TG-873870) (31) is a novel nonfluorinated quinolone developed from a series of 8-methoxy nonfluorinated quinolones (25). It lacks the characteristic fluorine at the sixth position in fluoroquinolones (FQs) (Fig. 1). Nemonoxacin is a potent antibacterial agent with broad-spectrum activity against clinical isolates and reference strains in both in vitro studies and experimental infections in animals. It is active against Gram-positive, Gram-negative, and atypical pathogens, including penicillin-and quinolone-resistant Streptococcus pneumoniae (PRSP and QRSP), methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant MRSA (QR-MRSA), and vancomycin-resistant enterococci (4, 17). The nemonoxacin MIC 90 range is 0.06 to 1 g/ml for MRSA clinical isolates and 0.03 to 1 g/ml for PRSP clinical isolates from North America and Taiwan (17, 24, 33). For QR-MRSA clinical isolates, the MIC 90 range is 1 to 2 g/ml; this is 4-to 64-fold lower than the MIC 90 s of FQs in parallel testing, including ciprofloxacin, levofloxacin, and moxifloxacin (17, 24). There is increasing concern about vancomycin-intermediate S. aureus (VISA) among clinical isolates. Nemonoxacin showed an MIC 90 of 2 g/ml against heterogeneous VIS...