Determination of a novel nonfluorinated quinolone, nemonoxacin, in human feces and its glucuronide conjugate in human urine and feces by high-performance liquid chromatography-triple quadrupole mass spectrometry
He G.,Fudan University |
He G.,Key Laboratory of Clinical Pharmacology of Antibiotics |
Guo B.,Fudan University |
Guo B.,Key Laboratory of Clinical Pharmacology of Antibiotics |
And 11 more authors.
Three methods were developed and validated for determination of nemonoxacin in human feces and its major metabolite, nemonoxacin acyl-β- d-glucuronide, in human urine and feces. Nemonoxacin was extracted by liquid-liquid extraction in feces homogenate samples and nemonoxacin acyl-β- d-glucuronide by a solid-phase extraction procedure for pretreatment of both urine and feces homogenate sample. Separation was performed on a C18 reversed-phase column under isocratic elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. Both analytes were determined by liquid chromatography-tandem mass spectrometry with positive electrospray ionization in selected reaction monitoring mode and gatifloxacin as the internal standard. The lower limit of quantitation (LLOQ) of nemonoxacin in feces was 0.12μg/g and the calibration curve was linear in the concentration range of 0.12-48.00μg/g. The LLOQ of the metabolite was 0.0010μg/mL and 0.03μg/g in urine and feces matrices, while the linear range was 0.0010-0.2000μg/mL and 0.03-3.00μg/g, respectively. Validation included selectivity, accuracy, precision, linearity, recovery, matrix effect, carryover, dilution integrity and stability, indicating that the methods can quantify the corresponding analytes with excellent reliability. The validated methods were successfully applied to an absolute bioavailability clinical study of nemonoxacin malate capsule. © 2014 John Wiley & Sons, Ltd. Source
TaiGen Biotechnology Co. | Date: 2014-09-30
A method of mobilizing cells expressing the type 4 CXC chemokine receptor into the peripheral circulation by contacting them with an effective amount of a compound of formula (I) shown below (each variable in the formula being defined in the Specification): The method can be used to treat cancer and myocardial infarction.
TaiGen Biotechnology Co. | Date: 2011-01-19
This invention relates to compounds of Formula (I), (II), or (III) shown in the specification. These compounds can be used to treat hepatitis C virus infection.
Hsu W.-T.,National Taiwan University |
Hsu W.-T.,National Health Research Institute |
Jui H.-Y.,National Taiwan University Hospital |
Huang Y.-H.,TaiGen Biotechnology Co. |
And 9 more authors.
Interaction between chemokine stromal cell-derived factor 1 and the CXC chemokine receptor 4 (CXCR4) governs the sequestration and mobilization of bone marrow stem cells. We investigated the therapeutic potential of TG-0054, a novel CXCR4 antagonist, in attenuating cardiac dysfunction after myocardial infarction (MI). In miniature pigs (minipigs), TG-0054 mobilized CD34+CXCR4+, CD133+CXCR4+, and CD271+CXCR4+ cells into peripheral circulation. After isolation and expansion, TG-0054-mobilized CD271+ cells were proved to be mesenchymal stem cells (designated CD271-MSCs) since they had trilineage differentiation potential, surface markers of MSCs, and immunosuppressive effects on allogeneic lymphocyte proliferation. MI was induced in 22 minipigs using balloon occlusion of the left anterior descending coronary artery, followed by intravenous injections of 2.85 mg/kg of TG-0054 or saline at 3 days and 7 days post-MI. Serial MRI analyses revealed that TG-0054 treatment prevented left ventricular (LV) dysfunction at 12 weeks after MI (change of LV ejection fraction from baseline, −1.0 ± 6.2% in the TG-0054 group versus −7.9 ± 5.8% in the controls). The preserved cardiac function was accompanied by a significant decrease in the myocardial expression of TNF-α, IL-1β, and IL-6 at 7 days post-MI. Moreover, the plasma levels of TNF-α, IL-1β, and IL-6 were persistently suppressed by the TG-0054 treatment. Infusion of TG-0054-mobilized CD271-MSCs reduced both myocardial and plasma cytokine levels in a pattern, which is temporally correlated with TG-0054 treatment. This study demonstrated that TG-0054 improves the impaired LV contractility following MI, at least in part, by mobilizing MSCs to attenuate the postinfarction inflammation. This insight may facilitate exploring novel stem cell-based therapy for treating post-MI heart failure. © 2015 Cognizant Comm. Corp. Source
Liu Y.,Fudan University |
Liu Y.,China Key Laboratory of Clinical Pharmacology of Antibiotics |
Zhang Y.,Fudan University |
Zhang Y.,China Key Laboratory of Clinical Pharmacology of Antibiotics |
And 25 more authors.
Journal of Microbiology, Immunology and Infection
Background/Purpose: To compare the clinical efficacy and safety of nemonoxacin with levofloxacin in treating community-acquired pneumonia (CAP) in a Phase II clinical trial. Methods: One hundred ninety-two patients with CAP were randomized to receive oral nemonoxacin (500 mg or 750 mg) or levofloxacin (500 mg) once daily for 7-10 days. Clinical and bacteriological responses were determined at the test of cure (TOC) visit in the full analysis set (FAS). Results: The clinical cure rate of nemonoxacin (500 mg), nemonoxacin (750 mg), and levofloxacin (500 mg) was 93.3%, 87.3%, and 88.5%, respectively, in the FAS (n = 168), and 93.0%, 93.9%, and 88.9%, respectively in the per protocol set (n = 152). At the TOC visit, nemonoxacin at 500 mg and 750 mg was proven to be noninferior to levofloxacin at 500 mg in the FAS in terms of clinical efficacy. The overall bacteriological success rate was 83.3% in both nemonoxacin groups and 80.0% in the levofloxacin 500 mg group in the bacteriological FAS. The comprehensive efficacy rate was comparable among the three groups (87.5% for the nemonoxacin 500 mg group, 93.8% for the nemonoxacin 750 mg group, and 81.3% for the levofloxacin 500 mg group). Most drug-related adverse events were mild and transient, mainly gastrointestinal symptoms such as nausea and vomiting, transient neutropenia, and elevated liver enzymes. No drug-related serious adverse events occurred. Conclusion: 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. © 2015. Source