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      Evaluation of Moxifloxacin-induced Biochemical Changes in Mice

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          Abstract

          The aim of the present study was to investigate the toxicological effects of moxifloxacin in mice to determine the toxicological implications. Forty mice of both sexes were divided into four groups of 10 mice each, designated as A, B, C and D. Group A served as the control and received 2 ml of distilled water, while Groups B, C and D were orally administered 12.5, 25 and 50 mg/kg body weight of moxifloxacin once daily for 7 days, respectively. The weights of the mice were recorded before and throughout the duration of drug administration. Blood samples were collected for serum analysis. Total blood protein, cholesterol, triglyceride, creatinine, activities of aspartate transaminase, alanine transaminase and alkaline phosphatase, levels of high density lipoprotein-cholesterol and low density lipoprotein-cholesterol were assayed. There were significant ( P≤0.05) differences in the concentrations of serum creatinine, urea, aspartate transaminase, alanine transaminase and alkaline phosphatase, levels of high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, cholesterol and triglyceride of mice administered moxifloxacin. Serum level of total bilirubin in low dose treated animals was not significantly different from that of the control group animals, but there were significant dose dependent decrease in the animals treated with 25 mg/kg as well as 50 mg/kg. Data of the study indicate there was a dose dependent reduction in the protein metabolites, lipid profile and liver enzyme activities of mice administered moxifloxacin.

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          Most cited references31

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          An outbreak involving extensive transmission of a virulent strain of Mycobacterium tuberculosis.

          From 1994 to 1996, there was a large outbreak of tuberculosis in a small, rural community with a population at low risk for tuberculosis. Twenty-one patients with tuberculosis (15 with positive cultures) were identified; the DNA fingerprints of the 13 isolates available for testing were identical. To determine the extent of transmission, we investigated both the close and casual contacts of the patients. Using a mouse model, we also studied the virulence of the strain of Mycobacterium tuberculosis that caused the outbreak. The index patient, in whom tuberculosis was diagnosed in 1995; the source patient, in whom the disease was diagnosed in 1994; and a patient in whom the disease was diagnosed in 1996 infected the other 18 persons. In five, active disease developed after only brief, casual exposure. There was extensive transmission from the three patients to both close and casual contacts. Of the 429 contacts, 311 (72 percent) had positive skin tests, including 81 [corrected] with documented skin-test conversions. Mice infected with the virulent Erdman strain of M. tuberculosis had approximately 1000 bacilli per lung after 10 days and about 10,000 bacilli per lung after 20 days. In contrast, mice infected with the strain involved in the outbreak had about 10,000 bacilli per lung after 10 days and about 10 million bacilli per lung after 20 days. In this outbreak of tuberculosis, the growth characteristics of the strain involved greatly exceeded those of other clinical isolates of M. tuberculosis. The extensive transmission of tuberculosis may have been due to the increased virulence of the strain rather than to environmental factors or patient characteristics.
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            Enzymatic determination of total cholesterol in serum.

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              Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man.

              The pharmacokinetics of moxifloxacin and its metabolites M1 (sulpho-compound) and M2 (acyl-glucuronide) were characterized in 12 healthy male volunteers in an open, randomized, crossover study. After an overnight fast the volunteers were given a single 400 mg dosage of moxifloxacin either as a tablet or a 1 h infusion with a washout phase of at least 1 week between the two treatments. Multiple plasma, faeces and urine samples were collected for the analysis of moxifloxacin and metabolites using validated HPLC with fluorescence detection. The AUC for both formulations was comparable with bioequivalence criteria fulfilled, with Cmax after oral treatment approximately 31% lower. Following oral administration, absorption was fast with low to medium variability (mean dissolution and absorption time 2.4 h). The absolute bioavailability was 86%. The excretion of moxifloxacin and its metabolites was quantified in a subset of eight subjects. More than 96% of the dose was recovered from urine and faeces after oral dosing, and >98% following i.v. administration of the drug. M1, which is strongly bound to plasma proteins (90%), was mainly eliminated into faeces (approximately 37-38% of the administered dose) and to a minor extent into urine (2.5% of the administered dose) by active tubular secretion. M2 (only 5% bound to plasma protein) was only found in urine, where it amounted to approximately 14% of the dose. Plasma concentrations of the metabolites were much lower than those of the parent compound. Moxifloxacin was well tolerated with few adverse events and no clinically relevant changes in laboratory values.
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                Author and article information

                Journal
                Indian J Pharm Sci
                Indian J Pharm Sci
                IJPhS
                Indian Journal of Pharmaceutical Sciences
                Medknow Publications & Media Pvt Ltd (India )
                0250-474X
                1998-3743
                Sep-Oct 2012
                : 74
                : 5
                : 454-457
                Affiliations
                [1]Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, P. M. B 12003, Lagos, Nigeria
                [1 ]Department of Biochemistry, College of Medicine, University of Lagos, P. M. B 12003, Lagos, Nigeria
                Author notes
                [* ] Address for correspondence E-mail: graceukpo@ 123456yahoo.com
                Article
                IJPhS-74-454
                10.4103/0250-474X.108422
                3660873
                23716875
                5406c3be-3439-4f16-95ba-155578d751ee
                Copyright: © Indian Journal of Pharmaceutical Sciences

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 October 2011
                : 31 August 2012
                : 06 September 2012
                Categories
                Short Communication

                Pharmacology & Pharmaceutical medicine
                blood chemistry,liver enzymes,mice,moxifloxacin
                Pharmacology & Pharmaceutical medicine
                blood chemistry, liver enzymes, mice, moxifloxacin

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