Effect Of Moxifloxacin Research Articles

Some Pharmacogical Adverse Effects of Moxifloxacin and Staphylococcal Aureus in Rats

Moxifloxacin is a broad spectrum fluoroquinolone antibacterial agent. We examined the plasma biomarkers of hepatorenal adverse effects of moxifloxacin ,lipid profile and blood glucose in rat following administration of moxifloxacin (MXF). Thirty-six Wistar rats, 200–250 g, were randomized into four groups (I–IV). Animals in group I (control) received 3.3 mL of distilled water, while animals in groups II administrated with moxifloxacin received 3.3 mL each of MXF equivalent to 26.4 mg/kg b.wt respectively for five successive days, III while animals in this group experimentally infected with staphylococcal aureus, and IV while animals in this group first experimentally infected with staphylococcal infection then received 3.3 mL each of moxifloxacine equivalent to 26.4 mg/kg b.wt respectively for five successive days. After seven days, plasma urea, bilirubin, and creatinine were significantly elevated in the MXF-treated animals. Activities of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were significantly increased in the plasma of MXF-treated animals compared to control. Also plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides increased significantly in the MXF-treated groups relative to control. Moreover, a significant increase in serum glucose concentration ,a significant decrease in blood Hb concentration and white blood cells)WBCs concentration (key words,MXF moxifloxacin ,HDL high density lipoprotein ,LDL low density lipoprotein .

Effects of moxifloxacin on the proarrhythmic surrogate markers in healthy Filipino subjects: Exposure-response modeling using ECG data of thorough QT/QTc study

Effects of moxifloxacin on QTc as well as proarrhythmic surrogate markers including J-Tpeakc, Tpeak-Tend and short-term variability (STV) of repolarization were examined by using both standard E14 time-based evaluation and exposure-response modeling. The study was conducted with a single-blind, randomized, single-dose, placebo-controlled and two-period cross-over design in healthy Filipino subjects. QT interval was corrected by Fridericia's formula (QTcF). In the E14 time-based evaluation of ECG data, the largest ΔΔQTcF with 90% confidence interval was 14.1 ms (11.2–16.9) with Cmax of 3.39 μg/mL at 3 h post-dose (n = 69; male: 35, female: 34), indicating a positive effect on the QTcF. Moxifloxacin significantly increased the ΔΔJ-Tpeakc and ΔΔTpeak-Tend, whereas the ΔΔSTV was not altered. Meanwhile in the exposure-response modeling of the same ECG data, the slope of moxifloxacin plasma concentration-ΔΔQTcF relationship was 4.84 ms per μg/mL and the predicted ΔΔQTcF with 90% confidence interval was 13.8 ms (13.1–15.1) at Cmax, also indicating a positive effect on the QTcF. Importantly, results in each proarrhythmic surrogate marker obtained by the exposure-response modeling also showed high similarity to those obtained by the E14 statistical evaluation. Thus, these results of moxifloxacin may become a guide to estimate proarrhythmic potential of new chemical entities.

The effect of radiolabeled antibiotics on biofilm and microorganism within biofilm

The aim of this study was to investigate the 131I and 127I labeled linezolid and moxifloxacin effects of minimum inhibitory concentration, and minimum bactericidal concentration on mature biofilm and microorganism within the biofilm. Linezolid and moxifloxacin were labeled with 131I and 127I and chromatography studies were carried out with thin layer radiochromatograpy and high-pressure liquid radiochromatography techniques. Specific activities of radiolabeled LZD and MXF was found to be 53.3 ± 3.1 and 127.3 ± 1.1 MBq/µmol for [131I]LZD and 7.6 ± 0.02 and 55.6 ± 0.8 MBq/µmol for [131I]MXF, respectively. The minimum inhibitory concentration and Time-Kill of Linezolid and moxifloxacin alone and their 131I and 127I labeled forms were tested with a standard strain of meticillin-susceptible Staphylociccus aureus. MIC values of LNZ and MXF were 2.96 nmol/mL (1 µg/ml) and 0.141 nmol/mL (0.062 µg/ml). Time Kills of MXF and LZD were found to be 0.06 and 1 μg, respectively. Antibiotics labeled with beta-emitting radioactive molecule may be a new theranostics strategy for biofilm infections.

Effect of moxifloxacin on QTc interval in adults with pulmonary tuberculosis.

Effect of moxifloxacin on QTc interval in adults with pulmonary tuberculosis.

Effect of moxifloxacin on oxidative stress, paraoxonase-1 (PON1) activity and efficacy of treatment in patients with multiple drug-resistant tuberculosis

Purpose: To investigate the effect of moxifloxacin on paraoxonase-1 (PON1) activity, and serum oxidative stress in patients with multiple drug-resistant tuberculosis (MDR-TB).Methods: A total ofof 130 MDR-TB patients who were treated with moxifloxacin from October 2014 to October 2010 in Eastern Medical District of Linyi People's Hospital of Shandong Province, China were randomly divided into an observation group (65 cases, moxifloxacin group) and control group (65 cases, non-moxifloxacin group). Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), PON1 levels and treatment efficacy for groups were determined.Results: Compared with pre-treatment levels, TOS (23.3 ± 4.7 vs 13.9 ± 3.3 umol H2O2 Eq/L, t = 13.20, p = 0.00) and OSI (17.4 ± 4.8 vs 5.7 ± 1.4 U, t = 18.87, p = 0.00) of the observation group significantly decreased, while TAS (1.4 ± 0.5 vs 3.5 ± 0.7 umol Trolox Eq/L, t = 19.68, p = 0.00) and PON1 (15.5 ± 6.9 vs 31.1 ± 8.3 U/L, t = 11.65, p = 0.00) significantly increased. TOS (23.3 ± 4.7 vs 13.9 ± 3.3 umol H2O2 Eq/L, t = 7.73, p < 0.05) and OSI (16.9 ± 5.5 vs 7.4 ± 3.2U, t = 12.04, p = 0.05) reduced significantly in the control group. Moxifloxacin correlated positively with △TAS (r = 0.697, p = 0. 04) and △PON1 (r = 0.785, p = 0.01), but correlation with △TOS (r = -0.625, p = 0.01) was negative. Efficacy was significantly higher in the observation group than that in the control group (81.54 % vs 56.92 %, p =0.00).Conclusion: Oxidative stress injury in MDR-TB patients may be effectively managed by combination of moxifloxacin with anti-TB treatmentKeywords: Multiple drug-resistant TB, Moxifloxacin, Paraoxonase, Oxidative stress

Moxifloxacin Increases Heart Rate in Humans.

(1) Background: We assessed the effect of moxifloxacin on heart rate, and reviewed the heart rate effects of other antibiotics; (2) Methods: A total of 335 normal volunteers had 12-lead electrocardiograms recorded at multiple time points before and during treatment with moxifloxacin and with placebo in seven consecutive, thorough QT studies of crossover design; (3) Results: The average baseline heart rate across the seven studies was 61.5 bpm. The heart rate after moxifloxacin dosing was analyzed at five time points shared by all seven studies (hours 1, 2, 3, 12 and 24). The maximum mean heart rate (HR) increase for the seven studies combined was 2.4 bpm (95% CI 1.6, 3.3) at hour 2. The range of mean maximum increases among the seven studies was 2.1 to 4.3 bpm. For the seven studies combined, the increase was statistically significant at all but the 24 h time point. The maximum observed individual increase in HR was 36 bpm and the mean maximum increase was 30 ± 4.1 bpm by time point and 8 ± 6.9 bpm by subject. Many antibiotics increase HR, some several-fold more than moxifloxacin. However, clinicians and clinical investigators give little attention to this potential adverse effect in the medical literature; (4) Conclusions: The observed moxifloxacin-induced increase in HR is large enough to be clinically relevant, and it is a potentially important confounder in thorough QT studies using moxifloxacin as an active control. More attention to heart rate effects of antibiotics is warranted.

Population Pharmacokinetic–Pharmacodynamic Analysis to Compare the Effect of Moxifloxacin on QT Interval Prolongation Between Healthy Korean and Japanese Subjects

PurposeThe goal of this study was to evaluate the moxifloxacin-induced QT interval prolongation in healthy male and female Korean and Japanese volunteers to investigate interethnic differences. MethodsThis multicenter, randomized, double-blind, placebo-controlled, 2-way crossover study was conducted in healthy male and female Korean and Japanese volunteers. In each period, a single dose of moxifloxacin or placebo 400 mg was administered orally under fasting conditions. Triplicate 12-lead ECGs were recorded at defined time points before, up to 24 hours after dosing, and at corresponding time points during baseline. Serial blood sampling was conducted for pharmacokinetic analysis of moxifloxacin. The pharmacokinetic–pharmacodynamic data between the 2 ethnic groups were compared by using a typical analysis based on the intersection-union test and a nonlinear mixed effects method. FindingsA total of 39 healthy subjects (Korean, male: 10, female: 10; Japanese, male: 10, female: 9) were included in the analysis. The concentration–effect analysis revealed that there was no change in slope (and confirmed that the difference was caused by a change in the pharmacokinetic model of moxifloxacin). A 2-compartment model with first-order absorption provided the best description of moxifloxacin’s pharmacokinetic parameters. Weight and sex were selected as significant covariates for central volume of distribution and intercompartmental clearance, respectively. An Emax model (E[C]=[Emax⋅C]/[EC50+C]) described the QT interval data of this study well. However, ethnicity was not found to be a significant factor in a pharmacokinetic–pharmacodynamic link model. ImplicationsThe drug-induced QTc prolongations evaluated using moxifloxacin as the probe did not seem to be significantly different between these Korean and Japanese subjects. ClinicalTrials.gov identifier: NCT01876316.

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

Drug-drug interactions between moxifloxacin and rifampicin based on pharmacokinetics in vivo in rats.

Moxifloxacin and rifampicin are all the first-line options for the treatment of active tuberculosis, which are often combined for the treatment of multidrug resistance pulmonary tuberculosis in clinic. However, the potential drug-drug interactions between moxifloxacin and rifampicin were unknown. The aim of this study was to investigate the drug-drug interactions between moxifloxacin and rifampicin based on their pharmacokinetics in vivo after oral administration of the single drug and both drugs, and reveal their mutual effects on their pharmacokinetics. Eighteen male Sprague-Dawley rats were randomly assigned to three groups: moxifloxacin group, rifampicin group and moxifloxacin + rifampicin group. Plasma concentrations of moxifloxacin and rifampicin were determined using LC-MS at the designated time points after drug administration, and the main pharmacokinetic parameters were calculated. In addition, effects of moxifloxacin and rifampicin on their metabolic rate and absorption were investigated using rat liver microsome incubation systems and Caco-2 cell transwell model. The main pharmacokinetic parameters of moxifloxacin including Tmax , Cmax , t1/2 and AUC(0-t) increased more in the moxifloxacin + rifampicin group than in the moxifloxacin group, but the difference was not significant (p > 0.05). However, the pharmacokinetic parameters of rifampicin, including peak concentration, area under the concentration-time curve, half-life and the area under the first moment plasma concentration-time curve, increased significantly (p < 0.05) compared with the rifampicin group, and the time to peak concentration decreased significantly (p < 0.05). The mean residence time of rifampicin also increased in moxifloxacin + rifampicin group compared with the rifampicin group, but the difference was not significant (p > 0.05). The rat liver microsome incubation experiment indicated that moxifloxacin could increase the metabolic rate of rifampicin from 23.7 to 38.7 min. However, the Caco-2 cell transwell experiment showed that moxifloxacin could not affect the absorption rate of rifampicin. These changes could enhance the drug efficacy, but they could also cause drug accumulation, which might induce adverse effect, so it was suggested that the drug dosage should be adjusted and the drug concentration in plasma should be monitored if moxifloxacin and rifampicin are co-administered. Copyright © 2016 John Wiley & Sons, Ltd.

Can an early phase clinical pharmacology study replace a thorough QT study? Experience with a novel H3-receptor antagonist/inverse agonist.

The objective of the present study was to compare the effects of pitolisant on QTcF interval in a single ascending dose (SAD) study and a thorough QT (TQT) study. The SAD study at three dose levels of pitolisant enrolled 24 males and the TQT study at two dose levels 25 males. Both studies intensively monitored ECGs and pitolisant exposure. Effect on QTcF interval was analysed by Intersection Union Test (IUT) and by exposure-response (ER) analysis. Results from the two studies were compared. In both studies, moxifloxacin effect established assay sensitivity. IUT analysis revealed comparable pitolisant-induced maximum mean (90 % confidence interval (CI)) placebo-corrected increase from baseline (ΔΔQTcF) in both the studies, being 13.3 (8.1; 18.5) ms at 200-mg and 9.9 (4.7; 15.1) ms at 240-mg doses in SAD study and 5.27 (2.35; 8.20) ms at 120-mg dose in TQT study. ER analysis revealed that ER slopes in SAD and TQT studies were comparable and significantly positive (0.031 vs 0.027 ms/ng/mL, respectively). At geometric mean concentrations, bootstrap predicted ΔΔQTcF (90 % CI) were 9.23 (4.68; 14.4) ms at 279 ng/mL (240-mg dose) in the SAD study and 4.97 (3.42; 8.19) ms at 156 ng/mL (120-mg dose) in the TQT study. Pitolisant lacked an effect of regulatory concern on QTc interval in both the studies, however analysed, suggesting that the results from the SAD study could have mitigated the need for a TQT study. Our findings add to the growing evidence that intensive ECG monitoring in early phase clinical studies can replace a TQT study.

HERG Protein Plays a Role in Moxifloxacin-Induced Hypoglycemia.

The purpose of this study was to investigate the effect of moxifloxacin on HERG channel protein and glucose metabolism. HERG expression was investigated using immunohistochemistry. The whole-cell patch clamp method was used to examine the effect of moxifloxacin on HERG channel currents. A glucose tolerance test was used to analyze the effects of moxifloxacin on blood glucose and insulin concentrations in mice. Results show that HERG protein was expressed in human pancreatic β-cells. Moxifloxacin inhibited HERG time-dependent and tail currents in HEK293 cells in a concentration-dependent manner. The IC50 of moxifloxacin inhibition was 36.65 μmol/L. Moxifloxacin (200 mg/kg) reduced blood glucose levels and increased insulin secretion in wild-type mice at 60 min after the start of the glucose tolerance test. In contrast, moxifloxacin did not significantly alter blood glucose and insulin levels in HERG knockout mice. Serum glucose levels increased and insulin concentrations decreased in HERG knockout mice when compared to wild-type mice. The moxifloxacin-induced decrease in blood glucose and increase in insulin secretion occurred via the HERG protein; thus, HERG protein plays a role in insulin secretion.

Rifampicin-moxifloxacin interaction in tuberculosis treatment: a real-life study.

Rifampicin (RMP) has been reported to reduce moxifloxacin (MFX) levels, which may interfere with the effectiveness of MFX in treating tuberculosis (TB). To study the MFX-RMP interaction in patients receiving MFX with or without RMP as part of their anti-tuberculosis treatment regimen. Patients with pulmonary TB followed up by the Tuberculosis Out-patient Clinic of the Pulmonary Department, Aristotle University of Thessaloniki, Greece, who underwent treatment with MFX during the periods 1 May 2012-30 April 2014 and 1 January-31 March 2015, were included in the study. MFX levels were compared between 12 patients who were receiving RMP (Group 1) and 10 who were not (Group 2). The participants did not significantly differ in body mass index, days of MFX treatment or MFX dose/kg. Neither the peak concentration (Cmax) nor the 24 h area under the curve (AUC24) differed significantly between the two groups (Group 1, Cmax median 3.9 [range 1.9-4.5] mg/l; AUC24 29.1 [10-47.4] mg·h/l and Group 2, Cmax 4.1 [2-6.4] mg/l; AUC24 36.5 [14.6-54.2] mg·h/l). Although a decrease in MFX exposure was observed in the RMP-treated group, the effect was lower than previously reported in a real-life setting. The large variability observed in MFX pharmacokinetics in both groups may suggest the need for dose readjustment in some patients, regardless of RMP co-administration.

Randomized, Controlled, Thorough QT/QTc Study Shows Absence of QT Prolongation with Luseogliflozin in Healthy Japanese Subjects.

Luseogliflozin is a selective sodium glucose co-transporter 2 (SGLT2) inhibitor. To evaluate the cardiac safety of luseogliflozin, a thorough QT/QTc study was conducted in healthy Japanese subjects. The effects of moxifloxacin on QT prolongation in Japanese subjects were also evaluated. In this double-blind, placebo- and open-label positive-controlled, 4-way crossover study, 28 male and 28 female subjects received a single dose of luseogliflozin 5 mg (therapeutic dose), luseogliflozin 20 mg (supratherapeutic dose), placebo, and moxifloxacin 400 mg. Serial triplicate digital 12-lead electrocardiograms (ECGs) were recorded before and after dosing, and results were analyzed using the Fridericia correction (QTcF) method. Serial blood sampling was performed for pharmacokinetic analyses of luseogliflozin and moxifloxacin to analyze the relationship between QTcF interval and plasma concentration. The upper limits of the two-sided 90% confidence intervals (CIs) for baseline and placebo-adjusted QTcF intervals (ΔΔQTcF) in the 5 mg and 20 mg luseogliflozin groups were less than 10 ms at all time points. No correlation between plasma luseogliflozin concentrations and ΔΔQTcF was observed. In the moxifloxacin group, the lower limits of the two-sided 90% CIs for ΔΔQTcF were greater than 5 ms at all time points. A positive relationship was observed between plasma moxifloxacin concentration and change in ΔΔQTcF. Luseogliflozin was well tolerated at both dose levels. The majority of adverse events were mild in severity, and no serious or life-threatening adverse events occurred. Neither therapeutic (5 mg) nor supratherapeutic (20 mg) doses of luseogliflozin affected QT prolongation in healthy Japanese subjects.

Pharmacokinetic-pharmacodynamic analysis to evaluate the effect of moxifloxacin on QT interval prolongation in healthy Korean male subjects.

A single 400 mg dose of moxifloxacin has been the standard positive control for thorough QT (TQT) studies. However, it is not clearly known whether a 400 mg dose is also applicable to TQT studies in Asian subjects, including Koreans. Thus, we aimed to develop a pharmacokinetic (PK)-pharmacodynamic (PD) model for moxifloxacin, to evaluate the time course of its effect on QT intervals in Koreans. Data from three TQT studies of 33 healthy male Korean subjects who received 400 and 800 mg of moxifloxacin and placebo (water) were used. Twelve-lead electrocardiograms were taken for 2 consecutive days: 1 day to record diurnal changes and the next day to record moxifloxacin or placebo effects. Peripheral blood samples were also obtained for PK analysis. The PK-PD data obtained were analyzed using a nonlinear mixed-effects method (NONMEM ver. 7.2). A two-compartment linear model with first-order absorption provided the best description of moxifloxacin PK. Individualized QT interval correction, by heart rate, was performed by a power model, and the circadian variation of QT intervals was described by two mixed-effect cosine functions. The effect of moxifloxacin on QT interval prolongation was well explained by the nonlinear dose-response (Emax) model, and the effect by 800 mg was only slightly greater than that of 400 mg. Although Koreans appeared to be more sensitive to moxifloxacin-induced QT prolongation than were Caucasians, the PK-PD model developed suggests that a 400 mg dose of moxifloxacin is also applicable to QT studies in Korean subjects.

Application of moxifloxacin in patients with multidrug-resistant tuberculosis

Objective To study the effect of moxifloxacin in the treatment of patients with multidrug-resistant tuberculosis .Methods 96 patients with multidrug-resistant tuberculosis were randomly divided into the two groups . The observation group（n=48 cases） was treated by moxifloxacin,and the control group（n=48 cases） was treated by levofloxacin.They were treated for 12 months.3,6,12 months after treatment,sputum smears were taken,and the adverse reactions were observed .Serum vasoactive intestinal peptide （ VIP） level was measured before and after treat-ment.Results 3,6,12 months after treatment,the sputum negative rates in the observation group were 36.0%, 87.5%,95.8%,which were significantly higher than 62.5%,77.1%,83.3% in the control group （χ2 =5.12, 5.96,7.28,all P〈0.05）.The total effective rate of the control group was 83.3%,which was significantly lower than 95.8%of the observation group （χ2 =5.28,P〈0.05）.Serum VIP levels in the control group and observation group were （29.3 ±6.7）ng/L,（20.7 ±5.4）ng/L.After treatment,the serum VIP levels in the two groups were significant-ly decreased,and the serum VIP level of the observation group was lower compared with the control group （t=3.01, P〈0.05）.During treatment,neutropenia,the incidence rates of gastrointestinal side effects ,liver damage and neuro-logical symptoms and other adverse reactions had no significant differences between the two groups （χ2 =1.56,1.74, 2.02,0.00,all P〉0.05）.Conclusion Moxifloxacin is better than levofloxacin in the treatment of patients with multidrug-resistant tuberculosis. Key words: Extensively drug-resistant tuberculosis; Tuberculosis,pulmonary; Moxifloxacin

Comparison of toxicities of moxifloxacin, cefuroxime, and levofloxacin to corneal endothelial cells in vitro

To evaluate and compare the toxic effects of moxifloxacin, cefuroxime, and levofloxacin on human corneal endothelial cells in vitro and determine the safe intracameral concentrations for them. Tottori University, Tottori, Japan. Experimental study. Human corneal endothelial cells in culture were exposed to moxifloxacin, cefuroxime, and levofloxacin at concentrations up to 2000 μg/mL. Evaluation of membrane damage was determined by ethidium homodimer-1 uptake and cell viability, by intrinsic esterase activity. The inhibitory effects of the 3 antibiotics on the constitutive secretion of interleukin-6 (IL-6) by human corneal endothelial cells were determined by enzyme-linked immunosorbent assay. The acute effects (6 hour) of the 3 antibiotics on membrane damage and cell death were dose-dependent for moxifloxacin and levofloxacin (≥ 500 μg/mL). For cefuroxime, membrane damage was not observed at 6 hours and only slight damage was detected at 24 hours at concentrations higher than 500 μg/mL. The half maximum inhibitory concentrations on cell viability of moxifloxacin, levofloxacin, and cefuroxime were 487 μg/mL, 578 μg/mL, and 1600 μg/mL, respectively. The inhibitory effects of the 3 antibiotics on the constitutive secretion of IL-6 were observed at 15.6 μg/mL or higher, indicating the antibiotics can impair the secretion of the protective cytokine even at low concentrations. Moxifloxacin at more than 500 μg/mL caused damage to the cell membranes of corneal endothelial cells; even higher concentrations decreased cell viability. Considering the lower minimum inhibitory concentration for inhibiting 90% growth by moxifloxacin, intracameral moxifloxacin at 500 μg/mL or less is recommended for prophylactic use. Dr. Inoue is a medical advisor to Alcon Japan Ltd. No author has a financial or proprietary interest in any material or method mentioned.

Toxicity and bioconcentration of the pharmaceuticals moxifloxacin, rosuvastatin, and drospirenone to the unionid mussel Lampsilis siliquoidea

Pharmaceuticals and personal care products (PPCPs) and their metabolites are continually released from wastewater treatment plants into the aquatic environment; however, their impact on aquatic biota is poorly understood. This study examined the toxicity and bioconcentration of three pharmaceuticals: moxifloxacin, rosuvastatin, and drospirenone to the unionid mussel Lampsilis siliquoidea. Effects of moxifloxacin and rosuvastatin were assessed through aqueous 21-d static-renewal tests using 2–year-old mussels, at 0.01, 0.1, 1, 10 and 100mg/L (nominal concentrations). Following exposure, survival, behavior, algal clearance rate, hemocyte viability and density, and glutathione S-transferase (GST) activity were assessed. In addition, the acute (48h) toxicity of moxifloxacin (0–100mg/L) and drospirenone (0–3mg/L) to glochidia (larval mussels) were examined. In 21day exposures (2-yr old mussels), there were no differences in survival, oxygen consumption, hemocyte density, or GST activity over the range of concentrations examined; however, the proportion of time mussels spent filtering, and consequently the algal clearance rate, decreased at the higher moxifloxacin and rosuvastatin concentrations. Bioconcentration factors (BCFs) ranged between 0.03 and 70 for moxifloxacin, and between 0 and 0.05 for rosuvastatin for exposures up to 100mg/L. The BCF for moxifloxacin at the highest exposure concentration was lower than that at the mid-level concentrations, likely due to decreased filtering activity at the higher exposure levels. The feeding rates declined and the amount of time the subadult mussels spent with their valves closed increased at the higher moxifloxacin and rosuvastatin exposures. Glochidia viability did not vary with exposure to drospirenone, but declined at the highest moxifloxacin concentration, resulting in an EC50 of 120mg/L. Overall, observed sublethal and lethal effects occurred at concentrations which exceed expected environmental concentrations through aqueous exposure, suggesting a low risk to freshwater mussels from these particular PPCPs.

The Effects of Moxifloxacin on QTc Interval in Healthy Korean Male Subjects

Background and objectiveMoxifloxacin 400 mg is a widely used positive control in thorough QT (TQT) studies, but its QT-prolonging effects in Korean subjects have not been studied. The present study was conducted to collect pilot data in Korean subjects after moxifloxacin administration to evaluate the adequacy of moxifloxacin as a positive control.MethodsThirty-eight, healthy, Korean, male subjects were recruited for pharmacokinetic (PK) blood sampling and electrocardiography (ECG) recordings at three different study sites. On day 1, a baseline 12-lead ECG was recorded, and on day 2, ECG recordings were conducted after placebo, or moxifloxacin 400- or 800-mg administration. Baseline-corrected, placebo-adjusted, corrected QT (ΔΔQTc) values were calculated. Blood samples were collected after moxifloxacin administration and PK parameters were assessed.ResultsA total of 33 subjects completed the study. The largest time-matched ΔΔQTc occurred approximately 4 h after dosing, with ΔΔQTcI (QT interval corrected by individual QT-RR regression model) values of 11.66 ms (moxifloxacin 400 mg) and 20.96 ms (800 mg). The mean and 90 % confidence intervals of ΔΔQTcI did not include zero at any of the measurement time points. There was a positive correlation between plasma moxifloxacin concentration and ΔΔQTcI (r = 0.422). Dose-proportional PK profiles were observed.ConclusionMoxifloxacin 400 mg is an adequate positive control in Korean TQT studies. Our results indicate that moxifloxacin 400 mg can be used to evaluate the cardiac safety of a drug in Korean subjects.

Dissecting the effect of moxifloxacin in mice with infected necrosis in taurocholate induced necrotizing pancreatitis

ObjectivesTo investigate the limited benefit of antibiotics in ameliorating the outcome of acute necrotizing pancreatitis, we analyzed antibiotic therapy in primarily infected necrotizing pancreatitis in mice with respect to the local pancreatic pathology as well as systemic, pancreatitis induced adverse events. MethodsSterile pancreatic necrosis (SN) was induced by retrograde injection of 4% taurocholate in the common bile duct of Balb/c mice. Primarily infected pancreatic necrosis (IN) was induced by co-injecting 108 CFU/ml Escherichia coli. 10 mg/kg of moxifloxacin was administered prior to pancreatitis induction (AN). After 24 h, animals were sacrificed to examine serum as well as organs for signs of SIRS. ResultsMoxifloxacin significantly reduced bacterial count in pancreatic lysates of animals with infected pancreatic necrosis (IN 4.1·107 ± 2.4·107 vs. AN 4.9·104 ± 2.6·104 CFU/g; p < 0.001). However, it did not alter pancreatic histology or pulmonary damage (Histology score: IN 23.8 ± 2.7 vs. AN 22.6 ± 1.7). Moxifloxacin reduced systemic immunoactivation (Serum IL-6: IN 330.5 ± 336.6 vs. 38.7 ± 25.5 pg/ml; p < 0.001), hypoglycemia (serum glucose: IN 105.8 ± 12.7 vs. AN 155.7 ± 39.5 mg/dl; p < 0.001), and serum aspartate aminotransferase (IN 606 ± 89.7 vs. AN 255 ± 52.1; p < 0.05). These parameters were significantly increased in animals with necrotizing pancreatitis. ConclusionIn the experimental setting, initial antibiotic therapy with moxifloxacin in acute infected necrotizing pancreatitis in mice does not have a beneficial impact on pancreatic pathology or pulmonary damage. However, other systemic complications induced by infected necrosis in acute pancreatitis are reduced by the administration of moxifloxacin.

Effect of moxifloxacin on survival, lipid peroxidation and inflammation in immunosuppressed rats with soft tissue infection caused by Stenotrophomonas maltophilia

In order to investigate the effect of moxifloxacin on survival, lipid peroxidation and inflammation in immunosuppressed rats with soft tissue infection caused by Stenotrophomonas maltophilia, 144 white male Wistar rats were randomized into six groups: Groups A and B received saline or moxifloxacin once per day, respectively; Groups C and D received saline or moxifloxacin twice per day, respectively, and Groups E and F received saline or moxifloxacin three times per day, respectively. Blood samples were taken at 6 and 30 hr after administration of S. maltophilia. Malonodialdehyde (MDA), WBC counts, bacterial tissue overgrowth, serum concentrations of moxifloxacin and survival were assessed. Survival analysis proved that treatment with moxifloxacin every 8 hr was accompanied by longer survival than occurred in any other group. Tissue cultures 30 hr after bacterial challenge showed considerably less bacterial overgrowth in the spleens and lungs of moxifloxacin-treated than in salinetreated animals, but not in their livers. At 6 hr there were no statistically significant differences between groups. However, at 30 hr, MDA concentrations were significantly greater (P = 0.044) and WBC counts significantly lower (P = 0.026) in group D than in group C. No statistically significant variations were observed between the other groups. Moxifloxacin possibly stimulates lipid peroxidation and enhances phagocytosis, as indicated by MDA production and survival prolongation, without being toxic, as indicated by WBC count. Therefore, under the appropriate conditions, moxifloxacin has a place in treatment of infections in immunosuppressed patients and of infections caused by S. maltophilia.