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What is already known about this subject • Although renal excretion is one important route of excretion of moxifloxacin and its metabolites, moxifloxacin pharmacokinetics are similar in patients with varying degrees of renal impairment (but not on dialysis) and in healthy subjects. What this study adds • This study showed that moxifloxacin pharmacokinetics are comparable in patients with severe renal failure requiring haemodialysis and in healthy subjects and patients with impaired renal function not on dialysis. • No dose adjustments are required for haemodialysis patients on oral moxifloxacin therapy. Aim We investigated single dose and steady-state pharmacokinetics of moxifloxacin in eight venovenous haemodialysis patients. Methods Plasma, dialysate and urine pharmacokinetic parameters for moxifloxacin and its main metabolites were calculated after single and multiple (7 days) dosing with 400 mg day−1. Results Moxifloxacin pharmacokinetics after a single dose and at steady state (multidose day 7) were comparable in patients with impaired renal function and healthy subjects (geometric mean/%CV AUC mg l−1 h single dose 37.0/24.3 in haemodialysis patients vs. 29.8/22.6 in healthy subjects, 95% CI for ratio of haemodialysis patients to healthy subjects 99.34%, 154.60%; steady state 40.4/29.1 haemodialysis patients vs. 33.9/20.1 in healthy subjects, 95% CI for ratio of haemodialysis patients to healthy subjects 90/39%, 156.93%). In haemodialysis patients plasma concentrations of moxifloxacin at steady-state were elevated compared with those after a single 400 mg dose (AUC mg l−1 h, geometric mean/%CV, 40.4/29.1) compared with 37.0/24.3; 95% CI for ratio of steady-state to single dose 87.29%, 136.52%, as were concentrations of metabolite M1 3.21/34.6 compared with 2.02/45.3, 95% CI for ratio of steady state to single dose 14.21%, 175.07%. Haemodialysis cleared about 9% of the dose as unchanged moxifloxacin. Conclusions No dose adjustments are required for venovenous haemodialysis patients on oral moxifloxacin therapy. [ABSTRACT FROM AUTHOR]

To evaluate the extent to which enterohepatic recycling circulation contributes to moxifloxacin bioavailability in healthy, males by administration of activated charcoal and to evaluate the efficacy of activated charcoal administration in decreasing systemic concentrations of moxifloxacin in the event of overdose.Nine healthy males, mean age 34 years (range 23–45 years) participated in a single centre, randomized, nonplacebo-controlled, three way crossover study. The pharmacokinetics of moxifloxacin in plasma and urine were determined for up to 96 h following a 400 mg single dose randomly administered on three separate occasions with a minimum washout phase of 1 week. Treatment A was 400 mg moxifloxacin IV as a 1 h infusion, treatment B was 400 mg moxifloxacin IV as a 1 h infusion with oral activated charcoal (5 g directly before the start of the infusion, 5 g immediately after the end of the infusion, and 10 g at 2, 4 and 8 h after the start of the infusion), treatment C was 400 mg oral moxifloxacin with activated charcoal (10 g 15 min before and at 2, 4 and 8 h after drug administration). The subjects underwent a series of clinical and laboratory tests.Single 400 mg doses of moxifloxacin (PO and/or IV) were safe and well tolerated. The bioavailability of moxifloxacin was significantly decreased when given with charcoal (AUC = 35.5 (IV reference)vs5.40 (PO)vs28.5 (IV) mg l−1 h). Concurrently peak concentrations were loweredCmax = 3.38 (IV reference)vs0.62(PO)vs2.97 (IV) mg l−1) by approximately 85% (P < 0.05) following oral administration and by 20% after IV treatment (P < 0.05). Bioavailability amounted to 15.4% (95% confidence interval 9.6, 25.0%) for treatment B while it was 80.4% (95% confidence interval 76.3.6, 84.6%) for treatment C. Terminal half-lives were not affected. The kinetics of urinary excretion corroborated these findings.The results of this study show that moxifloxacin undergoes pronounced enteric recycling after systemic uptake. In addition, these findings confirm that activated charcoal may be useful in treating moxifloxacin overdose by preventing its absorption. [ABSTRACT FROM AUTHOR]

Aims To evaluate the influence of impaired renal function on the plasma and urinary pharmacokinetics of moxifloxacin, a novel 8-methoxy-quinolone antibacterial drug. Methods Twenty male and 12 female subjects (8 healthy subjects, 24 patients with impaired renal function), 18–75 years of age were investigated in parallel fashion with four groups stratified according to creatinine clearance (CLCR ; n =8 for each group). The pharmacokinetics of moxifloxacin and the metabolites M1 (sulphonate metabolite) and M2 (glucuronide) in plasma and urine were determined repeatedly up to 96 h after single oral doses of 400 mg. Patients were monitored intensively with regard to clinical and laboratory safety and tolerability. Results Single doses of 400 mg moxifloxacin were safe and well tolerated. The urinary excretion of moxifloxacin (Aeur , P: 0.0002) and renal clearance (CLR , P <0.0001) were reduced with decreasing CLCR , mean C max was slightly reduced (C max -ratio 85.0%, 90% CI 67.9, 106.4% severe renal impairment vs healthy subjects) but the AUC was unchanged even in severe renal impairment (AUC-ratio 101.3%, 90% CI 79.7, 128.6%). The mean AUC of the N-sulphonate M1 was slightly increased (by about 53% for the most severe disease) by impaired renal function, but there was no significant correlation between individual AUC and CLCR , whilst Aeur and CLR were significantly correlated with CLCR . In contrast, for the acylglucuronide M2, Aeur (P: 0.0026), CLR (P <0.0001) and AUC (P: 0.0011) were directly correlated with CLCR . Conclusions Renal dysfunction had little effect on the plasma pharmacokinetics of either moxifloxacin or metabolite M1, although their renal clearance and urinary excretion were reduced. In contrast renal dysfunction did result in changes in the plasma pharmacokinetics of metabolite M2, causing greater... [ABSTRACT FROM AUTHOR]

We report a brief description of the interaction profile of moxifloxacin. After oral administration, the absorption of moxifloxacin was unaffected by ranitidine or by food consumption. Drugs containing multivalent cations (e.g., Mg[sup ++], Al[sup +++], and Fe[sup ++], but not Ca[sup ++]) impaired absorption. No clinically relevant effect of moxifloxacin was seen on the pharmacokinetics of digoxin under combination steady state conditions. Also, moxifloxacin did not affect the pharmacokinetics of theophylline or vice versa. This result, plus further data proving lack of interaction with glyburide, warfarin, and oral contraceptives, confirms the absence of metabolic interactions involving the cytochrome P-450 system, as previously reported. Concomitant administration of probenecid did not affect the elimination of moxifloxacin. Moxifloxacin thus has a unique drug interaction profile that is advantageous for its safe use. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of concomitant administration of dairy products on the pharmacokinetics and tolerability of moxifloxacin. Design: This was a single-centre, randomised, controlled, nonblinded, 2-way crossover study in healthy volunteers. Participants: 12 healthy men (aged 25 to 46 years) were enrolled in the study. Methods: The plasma and urinary pharmacokinetics of moxifloxacin were investigated after single doses of moxifloxacin 400mg administered orally either under fasting conditions or immediately after 250g of yoghurt that was to be consumed within 15 minutes. There was a 1-week interval between the study periods. Results: Administration of moxifloxacin after yoghurt had no effect on the extent of absorption, as estimated by the area under the plasma concentration-time curve from zero to infinity [AUC; geometric means 31.8 versus 33.9 mg/L · h after test and reference, respectively; estimated true treatment ratio 94%, 90% confidence interval (CI) 90 to 98%]. The rate of absorption was slightly decreased, with a slight reduction in maximum plasma concentration (C; geometric means 2.44 versus 2.87 mg/L; estimated true treatment ratio 85%, 90% CI 74 to 98%) and a prolonged time to reach C (t; median 2.75 versus 0.88 hours). The treatments were well tolerated in these healthy individuals. Conclusions: The effects of yoghurt on the pharmacokinetics of moxifloxacin are considered not clinically relevant. Hence, no special recommendations for administration are required when moxifloxacin is given together with dairy products. [ABSTRACT FROM AUTHOR]

Objective: To investigate the pharmacokinetics, safety and tolerability of moxifloxacin after single and repeated doses. Design and setting: This series comprised 3 separate placebo-controlled studies, 2 studies with a randomised crossover design (up to 400 mg/day) and 1 study with a group comparison design (600mg once daily). Patients and participants: Healthy male volunteers were included in these studies. Methods: Participants received 5-day treatment courses of moxifloxacin 100mg (n = 8) or 200mg (n = 8) twice daily or 400mg once daily (n = 7), or a 10-day treatment course of moxifloxacin 600mg once daily (n = 7). Pharmacokinetics were characterised after the first dose (24-hour profile) and the last dose (96-hour profile), with additional trough and peak measurements during the courses. Results: All treatments were well tolerated. No clinically relevant changes in the standard laboratory tests, vital signs or ECG were observed. Minimum plasma concentrations required to inhibit 90% of susceptible micro-organisms (e.g. 0.125 mg/L for Streptococcus pneumoniae) were attained rapidly and exceeded until the end of treatment. Repeated doses of 100 and 200mg twice daily and 400mg once daily resulted in stable trough and peak concentrations within 3 days of the first dose. The concentrations at steady state were moderately higher (approximately 30% for 400mg once daily) than after the first dose. Steady-state peak concentrations were between 0.9 mg/L (100mg twice daily) and 5.7 mg/L (600mg once daily). The terminal elimination half-life was 14 to 15 hours, supporting once daily administration of the drug. Accumulation ratios ranged between 87% for the lowest dosage and 111% after repeated doses of 600mg once daily, indicating the absence of clinically relevant accumulation due to non-linear pharmacokinetics. Across the studies, the average exposure after single and repeated doses was proportional to the dose administered. Conclusions: These studies indicate that, based on the safety profile and the pharmacokinetic behaviour of moxifloxacin, a dosage regimen of 400mg given once daily should be effective and well tolerated for the treatment of various infections. [ABSTRACT FROM AUTHOR]

Objective: To investigate the plasma and urinary pharmacokinetics, safety and tolerability of theophylline and moxifloxacin after single and repeated doses of either compound administered alone or concomitantly with the other. Design: This was a randomised, multiple-dose, period-balanced, 3-way crossover study in healthy volunteers. Participants: 12 nonsmoking healthy volunteers, 21 to 30 years of age were included in this study. Methods: The investigational medications, all given orally, were as follows: treatment A, moxifloxacin 200mg alone; treatment B, theophylline 400mg alone; treatment C, theophylline 400mg plus moxifloxacin 200mg. Each drug or combination was given twice daily on days 2 to 4 of the 5-day study period and as single morning doses on days 1 and 5. The study periods were separated by 1-week washout intervals. The plasma and urinary pharmacokinetics of moxifloxacin and theophylline were characterised after the first (morning of day 1) and eighth (morning of day 5) doses. Results: At steady state, the plasma pharmacokinetics of theophylline for treatments B and C proved equivalent in terms of maximum concentration (C) and bodyweight- and dose-normalised C [estimated true ratio 96%, 90% confidence interval (CI) 87 to 105%] and also in terms of area under the concentration-time curve from 0 to 12 hours (AUC) and normalised AUC (ratio 95%, 90% CI 85 to 107%); the median times to C (t) were also similar (5.0 and 6.0 hours for treatments B and C, respectively). The plasma pharmacokinetics of moxifloxacin for treatments A and C were equivalent with respect to C (estimated true ratio 109%, 90% CI 97 to 123%) and AUC (ratio 104%, 90% CI 100 to 108%); the median t values were also similar (0.5 and 1.0 hour for treatments A and C, respectively). The treatments were well tolerated. Conclusions: Moxifloxacin - in contrast to some older quinolones - does not interact pharmacokinetically with theophylline, confirming preclinical results on the absence of cytochrome P450-mediated metabolism. [ABSTRACT FROM AUTHOR]

Reviews the basic pharmacokinetic features of single intravenous and single and repeated oral doses of moxifloxacin in healthy volunteers. Methods; Results.

Investigates the influence of probenecid on the elimination of moxifloxacin. Methods; Results.