| BACKGROUND: Aminophylline is a double salt of theophylline and ethylenediamine. Theophylline,a blocker of purine receptors, belongs to methylpurine drugs. Theophylline can improve the respiratoryfunction, and the mechanism of the action is that theophylline can resist adenine on the contraction of therespiratory function, enhance force of diaphragmatic muscle contraction especially in the diaphragmaticmuscle unable to contract. Therefore, theophylline can strengthen heart beat, diuresis, expand coronaryartery, relax bronchial smooth muscle and excite central nervous system. In clinical, theophylline is mainlyused in the treatment of bronchial asthma, emphysema, bronchitis, and breathing difficulties. In veterinaryclinical, aminophylline is mainly in the treatment of symptomatic diseases caused by physical, chemical,virus, bacteria and other pathogenic microorganisms. In recent years, the further studies indicate thataminophylline is broad. can also be used to treat sleep apnea syndrome, premature infants asphyxia,arrhythmia, heart failure, nephrotic syndrome and acute nephritis, the application prospect of which isbroad. However, becaue of the complicated action mechanism, adverse reactions and poison phenomenoncan appear in the clinical application process. Therefore, it is particularly important to establish a scientificand reasonable method for guiding the clinical application of aminophylline. Pharmacokinetic is a commonmethod to study the regular of blood concentration changing by time which can be uesd to guide theclinical medication. Currently, pharmacokinetic research of aminophylline is mainly concentrated in people,rats and rabbits, while the relevant reports about this in chicken haven’t been seen until now. Thepharmacokinetic study of aminophylline in chicken can clarify the change rule of aminophylline in chickenand provide a reference for clinical using.OBJECTIVES: In order to gain a better understanding of the process: absorption, distribution,metabolism, eliminate and master the bioavailability accurately during oral dosing process ofaminophylline in healthy chicken, the author set up the high performance liquid chromatography （HPLC）method to study the pharmacokinetic of aminophylline in healthy chickens. The establishment of thismethod can not only guide the clinical application of in the process of preventing and controling diseases inchicken, but also can provide scientific basis for aminophylline to be used reasonablely. It is a newbreakthrough to broaden the application field of aminophylline.METHODS: In the experirnce, we use oral and intravenous two delivery ways, after that we shouldcollect blood samples through the vein under the wing at different time points. The blood samples will betested through HPLC method to study the pharmacokinetic characteristics and bioavailability ofaminophylline in healthy chickens.RESULTS: In the experiment, the acetaminophen is chosen as the internal standard, the chloroform-isopropanol （95:5, V/V） is chosen for liquid-liquid extraction processing of plasma samples. Plasmasamples processed can be tested in these conditions: C18chromatographic column from shimadzu （150x4.6mm, I.D.,5μm）, detection wavelength of274nm, mobile phase: methanol-water （25:75, V/V）, the flow rate:0.8ml/min, and the sample quantity:20μl. The retention time of aminophylline andacetaminophen respectively is7.33min and5.10min. Pharmacokinetic characteristics through oralaminophylline at the dose of10mg/kg in chicken can be shown in these parameters. Cmaxis （7.4±1.5）ug/ml, Tmaxis （1.83±1.11） h, t1/2is （11.65±1.14） h, keis （0.06±0.01） h-1, AUC0-tis （165.1±37.0） μg·h·mL-1, AUC0â†'∞is （179.3+35.6） μg·h·mL-1, MRT is （15.27±0.62） h, CLtotis （0.97±0.20）mL·min-1·kg-1, Vdis （0.97±0.22） L·kg-1; Pharmacokinetic characteristics through intravenousaminophylline at the dose of10mg/kg in chicken can also be shown like this. Cmaxis （16.9±3.01） ug/ml,Tmaxis （0.26±0.28） h, t1/2is （12.76±3.32） h, keis （0.06±0.01） h-1, AUC0-tis （219.1±25.3）μg·h·mL-1, AUC0â†'∞is （231.5±32.1） μg·h·mL-1, MRT is （13.98±0.79） h, CLtotis （0.73±0.10）mL·min-1·kg-1, Vdis （0.80±0.22） L·kg-1. The absolute bioavailability of oral administration is （75.6±15.7）%. The results of the experiment indicate that the elimination half-life of aminophylline in thechickenis longer, the removal rate is smaller, and the apparent volume of distribution is larger. The absolutebioavailability of aminophylline in chicken after oral administration is high, so oral administration canachieve a good clinical therapeutic effect. |
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