| Tuberculous pleurisy is one of the more common clinical type of extrapulmonary tuberculosis, as well as the more common reasons for the formation of pleural effusion.In recent years, with the increase of incidence of HIV/AIDS and other infectious diseases, the incidence of TB also has a tendency to rise, according to the latest TB research report, in 2013, about 9 million people worldwide suffer from tuberculosis, about 3-25% patients with tuberculous pleurisy, tuberculous pleural effusion is one of the types of tuberculous pleurisy, usually formed by dry pleurisy further development. Acute onset is often occur in young people, usually start soon,tuberculosis poisoning symptoms. Commonly used drug treatment is first-line anti-tb drugs other second-line anti-tb drugs, the method of moxifloxacin as a second-line anti-tb drugs in clinic often first-line anti-tb drugs in the treatment of tuberculous pleurisy, a study reported moxifloxacin first-line anti-tb drugs can shorten the treatment cycle of TB patients and this test plans to explore moxifloxacin in tuberculous pleurisy patients with pleural effusion(hereinafter referred to as pleural effusion, similarly hereinafter) and plasma of pharmacokinetic characteristics in order to provide reference for clinical rational use of moxifloxacin.ObjectiveThe aim of this study was to evaluate the pharmacokinetics and penetration of moxifloxacin(MXF) in patients with tuberculous pleural effusion.Materials and Methods(1)We used high performance liquid chromatography(HPLC) to determinate the concentration of moxifloxacin concentration in plasma of Tuberculous pleurisy. The determination was performed on Agilent Eclipse XDB-C18 column with mobile phase consisted of acetonitrile-water(0.05%TFA,22∶78)at the flow rate of 1.0 ml/min. UV detection wavelengths were set at 296 nm(0-2.5 min),256 nm(2.5-4.5 min)and 296nm( 4.5-8.0 min), respectively. The column temperature was 25℃ and injection volume was 20μL, internal standard method.(2)We used high performance liquid chromatography(HPLC) to determinate theconcentration of moxifloxacin concentration in Pleural effusion of Tuberculous pleurisy.The determination was performed on Agilent Eclipse XDB-C18 column with mobile phase consisted of acetonitrile-water(0.05%TFA,23:77)at the flow rate of 1.0 ml/min.UV detection wavelengths were set at 296 nm(0-2.5 min),256 nm(2.5-4.5 min)and296 nm(4.5-8.0 min),respectively. The column temperature was 30℃ and injection volume was 30μL, internal standard method.(3)Through the inclusion and exclusion criteria screening of 11 patients with tuberculous pleurisy, age 18 or above, any gender, selected patients within 2 weeks before study did not use any other antibacterial drugs, there is no history of drug allergy(especially the quinolones), 3 months before the test did not attend any other drug clinical trials.A general inspection and related laboratory tests, after physical examination to comply with relevant indicators, according to the dose of 400mg·d-1at8:00 in the morning and at the same time oral moxifloxacin and isoniazid(300mg·d-1),rifampicin(450mg·d-1), ethambutol(750mg·d-1) and pyrazinamide(1500mg·d-1).Experiments of avoid tea, wine and caffeinated beverages, avoid strenuous activity,avoid long time exposure under the strong light.During the whole test for the monitoring of drug safety and tolerability. After dosing 0, 1, 0.5, 0.5, 2, 3, 3.5, 4, 6, 8,12, 24 h respectively extracting venous blood 5 ml and 5 ml water, using HPLC determination of subjects of plasma and the drug concentration in the water.Results(1)In the range of 0.05~ 10μg·m L-1(r=0.9996), moxifloxacin showed a good linear relation in plasma by HPLC. The lower limit of quantitation( LLOQ) was0.05μg·m L-1. The inter-day RSD of low,medium and high concentration were 2.58%、2.12%and2.21%, and intra-day RSD were 5.64% 、 3.51% and3.73%. The extraction recovery of them were 67.67%、81.33%and83.18%,and internal standard were 97.31%(2)In the range of 0.1-10.00μg·m L-1(r=0.9992), moxifloxacin showed a good linear relation in Pleural effusion by HPLC. The lower limit of quantitation(LLOQ)was 0.1μg·m L-1. The inter-day RSD of low,medium and high concentration were 2.76%,2.23% and 2.22%, and intra-day RSD were 5.88%、3.49% and 3.60%. The extractionrecovery of them were 53.93%、63.42%and 65.42%,and internal standard were 91.51%.(3)A single 400 mg after moxifloxacin, pharmacokinetic parameters in plasma Cmax, Cthrough, Tmax and AUC0-24 were(4.599± 1.388) μg·m L-1,(0.621±0.287)μg·m L-1,(1.8±0.258) h and(45.127 ± 13.039) mg·h·L-1. pharmacokinetic parameters in Pleural effusion Cmax, Cthrough, Tmax and AUC0-24 were(3.252±0.967) μg·m L-1(0.869 ± 0.411) μg·m L-1,(3.6±0.394) h and(40.039 ± 14.340) mg·h·L-1.ConclusionUsing HPLC to determine the plasma and chest moxifloxacin concentration in water is simple, accurate and reproducible, and suitable for determination of tuberculous pleurisy patients chest moxifloxacin concentration determination of water.The determination of moxifloxacin in breast in the water concentration is far greater than the minimum bacteriostasis concentration, is conducive to moxifloxacin inhibit the growth of mycobacterium tuberculosis thoracic water.For clinical application of moxifloxacin in the treatment of tuberculous pleurisy.Key words:... |
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