Plasma Moxifloxacin Concentrations Research Articles

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.

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.

Susceptibility of rapidly growing mycobacteria isolated from cats and dogs, to ciprofloxacin, enrofloxacin and moxifloxacin

Rapidly growing mycobacteria (RGM) cause infections in cats and dogs which require prolonged antibacterial medication for resolution. In Australia, pathogens from the Mycobacterium fortuitum and Mycobacterium smegmatis clusters are responsible for most of the RGM infections in cats and dogs. As fluoroquinolones are often recommended for treating such infections, 14 M. fortuitum isolates, 51 isolates from the M. smegmatis cluster and 2 M. mageritense isolates, collected from feline and canine patients, underwent susceptibility testing to the second generation fluoroquinolones ciprofloxacin and enrofloxacin and the newer generation fluoroquinolone moxifloxacin. Using microbroth dilution, the MIC90 of ciprofloxacin, enrofloxacin, and moxifloxacin that inhibited growth of M. fortuitum isolates were 0.500, 0.250 and 0.063μg/mL respectively. For the M. smegmatis cluster isolates the corresponding MIC90 was 0.500, 0.250 and 0.125μg/mL respectively. E-test results showed similar trends but MICs were lower than those determined by microbroth dilution. Additionally, moxifloxacin was administered to 10 clinically normal cats (50mg per cat, once daily for 4 days). The plasma moxifloxacin concentration 2h after the last dose was determined by liquid chromatography as 2.2±0.6μg/mL. The plasma concentration at 2h:MIC90 ratios for moxifloxacin for M. fortuitum and M. smegmatis cluster was 34.9 and 17.6 respectively which exceeded the recommended threshold of 10, indicating that moxifloxacin has good theoretical efficacy for treatment of those M. fortuitum and M. smegmatis infections in cats and dogs that have become refractory to other antibacterial drug classes.

Pharmacokinetics of Moxifloxacin in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

To investigate the effect of continuous ambulatory peritoneal dialysis (CAPD) on plasma and peritoneal fluid concentration and pharmacokinetics of moxifloxacin after administration of one 400 mg dose orally to end-stage renal failure patients undergoing CAPD. Blood and peritoneal samples were collected from 8 patients at standard time intervals and concentrations of moxifloxacin were estimated by HPLC analysis with fluorometric and ultraviolet detection. Pharmacokinetic parameters were estimated using standard noncompartmental methods. Median maximum plasma moxifloxacin concentration was 5.86 mg/L at a median time of 1.25 hours. In serum, median area under the concentration-time curve (AUC(0-->inf)) was 157.95 +/- 100.34 mg.hour/L, median t(1/2) 25.00 hours, median clearance 2.54 L/hour, and median distribution volume 94.90 L. Median peritoneal fluid-to-plasma ratio of moxifloxacin ranged between 0.84 and 1.00, denoting adequate penetration and lack of considerable moxifloxacin removal during CAPD. Maximum moxifloxacin concentration/minimum inhibitory concentration (MIC) and AUC(0-->24)/MIC ratios were above the cutoff points that indicate clinical success. A single 400 mg oral dose of moxifloxacin is safe, presents rapid peritoneal fluid penetration, has similar plasma and peritoneal fluid pharmacokinetics, and should therefore be efficacious in the treatment of CAPD-induced peritonitis.

Plasma and Cerebrospinal Fluid Pharmacokinetics of Moxifloxacin in a Patient with Tuberculous Meningitis

Plasma and Cerebrospinal Fluid Pharmacokinetics of Moxifloxacin in a Patient with Tuberculous Meningitis

Vitreous and Aqueous Penetration of Orally Administered Moxifloxacin in Humans

To investigate intraocular penetration of moxifloxacin hydrochloride after oral administration. Prospective study of 15 patients scheduled for vitrectomy between September and November 2004 at the Barnes Retina Institute, St Louis, MO. Aqueous, vitreous, and serum samples were analyzed from 15 patients after oral administration of 2 tablets containing 400 mg of moxifloxacin. Assays were performed using high-performance liquid chromatography. The mean +/- SD moxifloxacin concentrations in plasma (n = 15), vitreous (n = 13), and aqueous (n = 13) samples were 3.56 +/- 1.31 microg/mL, 1.34 +/- 0.66 microg/mL, and 1.58 +/- 0.80 microg/mL, respectively. Mean +/- SD sampling times after oral administration of the second moxifloxacin tablet for plasma, vitreous, and aqueous were 2.94 +/- 0.81 hours, 3.77 +/- 0.92 hours, and 3.71 +/- 0.89 hours, respectively. The percentages of plasma moxifloxacin concentration in the vitreous and aqueous were 37.6% and 44.3%, respectively. Minimal inhibitory concentrations against 90% levels were exceeded against a wide spectrum of gram-positive and gram-negative pathogens in the vitreous and aqueous. Moxifloxacin has a spectrum of coverage that encompasses the most common organisms in endophthalmitis. The pharmacokinetic findings of this investigation reveal that orally administered moxifloxacin achieves therapeutic levels in the noninflamed eye. Because of their broad spectrum of coverage, low minimal inhibitory concentration against 90% levels, good tolerability, and excellent oral bioavailability, fourth-generation fluoroquinolones may represent a major advance for managing posterior segment infections.