antofloxacin and Bacterial-Infections

To find an appropriate dose regimen of the novel antibacterial agent antofloxacin for a phase II clinical trial using a population pharmacokinetic (PPK) study in healthy volunteers and the minimum inhibitory concentration (MIC) as pharmacodynamic (PD) parameters.. Twenty-four healthy volunteers were enrolled in a double-blind crossover study and received antofloxacin (200 or 400 mg/d, po) for consecutive 5 d with 10 d washout between two separate periods. Blood concentrations were analyzed using HPLC with a UV-Vis detector. The values of area under the curve (AUC) with covariates were obtained from a PPK model, and the MICs came from the previous in vitro studies. The dose regimen was determined for the phase II clinical trial according to the ratio (>20) of AUC/MIC, and the efficacy of the dose was evaluated by the trial.. A two-compartment model best described the time-concentration data with first-order absorption. The PPK parameter estimates for CL, V(c), Q, V(p) and K(A) are 8.34 L/h, 142 L, 15.9 L/h, 52.2 L and 4.64 1/h, respectively. The covariates sex for K(A), weight for CL, weight for V(c) and interoccasion variability were included in the final model. The AUC/MIC was calculated based on the PPK model and the MIC of antofloxacin for Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus and Staphylococcus epidermidis were determined in previous researches. The 400 mg loading dose with 200 mg/d maintenance dose was recommended and confirmed by the phase II trial.. The ratio of AUC from the PPK model vs MIC as the PD parameter can be applied in a dose-finding trial of antofloxacin in treatment of bacterial infections. The PPK model suggests that sex and body weight may be considerations in regards to individual therapy, which should be investigated in larger clinical trials and serve as a potential reference for clinical therapies.

Topics: Adult; Anti-Bacterial Agents; Area Under Curve; Bacteria; Bacterial Infections; Body Weight; Chromatography, High Pressure Liquid; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Microbial Sensitivity Tests; Models, Biological; Ofloxacin; Sex Factors; Young Adult

To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections.. A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was closed as controlled drug. The duration of treatment was 7-14 days in both groups.. A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for per-protocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS) population were 79.7% and 77.4%, the effective rates were 95.2% and 96.7%, and the bacterial clearance were 96.7% and 97.5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety. The drug adverse events occurred both in 10.1%, and drug adverse reactions occurred in 7.8% and 7.9% patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prolongation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P > 0.05).. Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Bacterial Infections; Double-Blind Method; Female; Humans; Levofloxacin; Male; Middle Aged; Ofloxacin; Young Adult