Pharmacokinetics Of Moxifloxacin Research Articles

Single- and Multiple-dose Pharmacokinetics of Oral Moxifloxacin and Clarithromycin, and Concentrations in Serum, Saliva and Faeces

Moxifloxacin and clarithromycin are important antibacterial drugs in the treatment of community-acquired respiratory tract infections. In a double-blind, randomized, 2-period cross-over study the pharmacokinetics of moxifloxacin versus clarithromycin were determined after single and multiple doses in 12 healthy male volunteers. The concentrations of the antibiotics in serum, saliva and faeces were measured by validated high-performance liquid chromatographic methods. In serum, moxifloxacin exhibited a mean peak concentration of 3.1 +/- 0.6 mg/l after a time to peak concentration of 1.67 +/- 0.96 h on day 1, with a significant increase to 3.98 +/- 1.10 mg/l on day 7 (p < 0.05). The area under the curve-12 revealed a highly significant increase from 28.2 + 4.1 mg*h/l on day 1 to 39.5 +/- 6.6 mg*h/l on day 7 (p < 0.01). There were also significant differences in terminal half-life between day 1 and day 7 [10.6 h (range 9.0-12.8) vs 14.9 h (range 12.6-28.1); p < 0.01] and in mean residence time (15.1 +/- 1.9 vs 18.2 +/- 2.4 h; p < 0.01). The concentrations of moxifloxacin in saliva were well equilibrated with serum at a relatively constant saliva-serum ratio of about 0.8. Pharmacokinetic parameters of clarithromycin and its metabolite, 14-hydroxy-clarithromycin, were similar to previously published data. Accumulation was found. No serious adverse events were observed with either study drug.

Absence of Drug Interaction between Oral Moxifloxacin and Intramuscular Morphine Sulfate in Healthy Volunteers

Objective To determine the effects of intramuscular morphine sulfate on the pharmacokinetics of moxifloxacin.

Comparative pharmacodynamics of moxifloxacin and levofloxacin in an in vitro dynamic model: prediction of the equivalent AUC/MIC breakpoints and equiefficient doses

To demonstrate the impact of the different pharmacokinetics of moxifloxacin and levofloxacin on their antimicrobial effects (AMEs), killing and regrowth kinetics of two clinical isolates of Staphylococcus aureus and one each of Escherichia coli and Klebsiella pneumoniae were studied. With each organism, a series of monoexponential pharmacokinetic profiles of single doses of moxifloxacin (T:1/2 = 12.1 h) and levofloxacin (T:(1/2) = 6.8 h) were simulated. The respective eight-fold ranges of the ratios of area under the concentration-time curve (AUC) to the MIC were 58-475 and 114-934. Species- and strain-independent linear relationships observed between the intensity of AME (I:(E)) and log AUC/MIC were not superimposed for moxifloxacin and levofloxacin (r(2) = 0.99 in both cases). The predicted AUC/MIC ratios for moxifloxacin and levofloxacin that might be equivalent to Schentag's AUC/MIC breakpoint for ciprofloxacin (125) were estimated at 80 and 130, respectively. The respective equivalent MIC breakpoints were 0.41 mg/L (for a 400 mg dose of moxifloxacin) and 0.35 mg/L (for a 500 mg dose of levofloxacin). Based on the I:(E)-log AUC/MIC relationships, equiefficient 24 h doses (D:(24)s) of moxifloxacin and levofloxacin were calculated for hypothetical strains of S. aureus, E. coli and K. pneumoniae with MICs equal to the respective MIC50s (weighted geometric means of reported values). To provide an 'acceptable' I:(E) = 200 (log cfu/mL)*h, the D:(24)s of moxifloxacin for all three organisms were much lower (150, 30 and 60 mg, respectively) than the clinically proposed 400 mg dose. Although the usual dose of levofloxacin (500 mg) would be in excess for E. coli and K. pneumoniae (D:(24) = 36 and 220 mg, respectively), it might be insufficient for S. aureus (the estimated D:(24) = 850 mg). Moreover, to provide the same effect as a 400 mg D:(24) of moxifloxacin against staphylococci, levofloxacin would have to be given in a 5000 mg D:(24), which is 10-fold higher than its clinically accepted dose. The described method of generalization of data obtained with specific organisms to other representatives of the same species might be useful to predict the AMEs of new quinolones.

Pharmacokinetics and metabolism of moxifloxacin.

Moxifloxacin is a recently developed fluoroquinolone antibiotic. It is rapidly absorbed following oral administration, reaching a mean peak drug plasma concentration (C(max)) of approximately 3.56 mg/l within 2 h after a 400 mg dose. The rate and extent of absorption are not significantly affected by food or elevated gastric pH. Moxifloxacin binds weakly to plasma proteins and penetrates well into most tissue and fluid compartments, with generally higher drug concentrations in tissue and fluid compartments than those observed in plasma. Moxifloxacin is metabolized to an N-sulfate conjugate and an acyl glucuronide in humans. The N-sulfate and the unchanged moxifloxacin are detected in plasma, urine and feces. The acyl-glucuronide is detected in plasma and urine, but not in feces. The plasma elimination half-life ranges from 8.2-15.1 h in healthy individuals. The urinary excretion of the unchanged drug accounts for 19-22% of the given dose. Neither renal nor hepatic impairment significantly affect the pharmacokinetics of moxifloxacin.

Pharmacokinetics of Moxifloxacin in Special Populations

Pharmacokinetics of Moxifloxacin in Special Populations

Advances in Bioanalytical Methodology Used to Characterise Clinical Pharmacokinetics of Moxifloxacin

Advances in Bioanalytical Methodology Used to Characterise Clinical Pharmacokinetics of Moxifloxacin

Basic Pharmacokinetics of Moxifloxacin

Basic Pharmacokinetics of Moxifloxacin

Pharmacokinetics of Moxifloxacin in A 5/6th Nephrectomized Rat Model

Moxifloxacin (MFLX) is a new 8-methoxyfluoroquinolone derivative with a broad spectrum of antibacterial activity. MFLX at doses of 200 and 400 mg was selected to conduct the pharmacokinetic study and the drug was given orally to control and nephrectomized rats. A 5/6th nephrectomized rat model was used in this study. The drug levels in the plasma were determined using a spectrofluorimetric assay. The pharmacokinetic parameters viz. peak plasma concentration (Cmax) and area under the curve (AUC0-8) of the nephrectomized and control rats were compared. The Cmax for both 200 and 400 mg dose of MFLX in nephrectomized rats showed significant difference(P&lt;0.001) from the control group, which reveals the changes in the Cmax of MFLX in renal failure. The AUC0-8 for both 200 and 400 mg dose of MFLX in nephrectomized rats differ significantly (P&lt;0.001) from sham operated control group, which implies the variation in MFLX availability in altered renal function. The AUC0-8 for 400 mg dose of MFLX in nephrectomized rats differ significantly from 200 mg dose of MFLX in nephrectomized group, which reveals that in higher dose, MFLX shows an abrupt increase in the drug availability in renal failure. It is conclude that preclinical drug monitoring of moxifloxacin in laboratory animals can be performed by using 5/6th nephrectomized rat models for determining the dose of MFLX for kidney failured patients. Various pharmacokinetic parameters determined differed in nephrectomised rats when compared to the control.