| Chronic obstructive pulmonary diseases(COPD), a common category of human respiratory disease with high morbidity, has become the fourth leading cause for death in the world. In clinical practice, the patients with COPD often receive the combined therapy of fluoroquinolones (FQLNs) and theophylline(TP).However, researches have shown that adverse effects of TP always accompany the combination of FQLNs and TP. Studies have revealed that FQNLs can restrain the metabolism of TP to different degrees. It reduces the clearance of TP, lengthened the elimination half-life time of TP which finally raised the serum concentration of TP. The principles of the influences of FQNLs on the pharmacokinetics of TP are not clear now. Many researchers hold at present that, as the inhibitor of rotating enzyme, the principles of the inhibition of FQNLs on the metabolism of TP mainly lie in the inhibition of one subclass of the cytochrome oxidase (CYP1A2). However studies have shown that xanthine drugs are metabolized by CYP1A2 in the liver chiefly, which further proves that the different degrees of fluoroquinolones' inhibition on hepatic cytochrome oxidase hampers the metabolism of TP, which is apt to accumulate intoxication.Doxophylline (Dox), a new-type xanthine drug, has recently been developed to treat COPD. Compared with TP, Dox boasts high curative effect and low poison, hi the treatment of bronchial spasm, Dox, which is ten to fifteen times as effective as TP, has the prospect of becoming the substitute of TP. Documents indicate that toxic concentration of Dox is beyond 20ugtaL , which is similar to TP. The phase II clinical practice indicates that the rates of occurance of the adverse effects of Dox and TP are 19.6% and 20.8% respectively, there is no notable statistical difference between them(P>0.05). Therefore, the researches of the influences of FQNLs on the pharmacokinetics of Dox are needed for directing the doctors to use drugs reasonably. Levofloxacin (LVFX) is the (L-) optical isomer of floxacin. It is widely used in clinical practice thanks to its advantage of more activity against bacteria and less adverse effect. However, the reports concerning the influence of LVFX on the pharmacokinetics of Dox are absent at home and abroad. This paper focuses on the influence when the two drugs are used together.Materials and Methods (1) This dissertation aims at the study of the pharmacokinetics of Dox alone and its combination with LVFX in healthy volunteers and patients. In healthy volunteers, the study is conducted by using a crosser design. In patients, it is done by using parallel design. (2) The concentration of Dox in blood is detected by high performance liquid chromatography(HPLC). Mobile phase:acetonitrile: 0.1M NaHPO buffer (15:85 v/v PH=6.7~6.9) consists of l%o triethypamine ; Flow rate: l.Oml/min; Ultraviolet wavelengh:273nm; column temperature:30癈. (3) All of the specimens are extracted by dichloromethane and isopropanol and are evaporated to dryness. The residue is reconstituted with mobile phase, and subjected to HPLC analysis. Dox in blood can be separated from the baseline very well by this method. After combination of LVFX, the chromatographic peak of Dox can be detected without any other interferences. The regression between concentration and peak height shows that Dox has a good linear relationship in the range of 0.05-8 U g/mL( Y =0.9999).The detecting method is stable with the average recovery of Dox 104.7% and is precise with the standard deviation among days below 8%, withindays below 5%. (4) The concentration-time data are disposed with 3P97programe.Results I The pharmacokinetics in healthy volunteers: Dox alone group: Dox 300mg ivgtt; Dox+LVFX group: LVFX 400mg ivgtt, followed by Dox 300mg ivgtt. The serum sample was collected at indicated time after the use of Dox .The results are as follows: (1) The concentration-time curve in Dox alone and combined groups are adequately fit to two-compartment open model;(2) The concentration of Dox in Dox alone and combined groups are: (5min) 3.13?.64...
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