Pharmacokinetic Study On Atomization Inhalation Furosemide In Healthy Mice

Objective: To construct the determination method of furosemide inplasma and pulmonary tissue of mice. To study the pharmacokinetic parameters of atomization inhalation furosemide in healthy mice and the relationship of the drug concentrations in plasma and pulmonary tissue homogenate liquid. From all above, we could provide data for further clinical research about atomization inhalation furosemide used in human asthma. Method: Divided the healthy mice into 2 groups in random. The high-dose group was given 0.155mg/20g atomization inhalation furosemide. Took out the plasma and pulmonary tissue at 0, 10, 20, 30, 45, 60, 90, 120, 150, 180min respectively (n=8). The low-dose group was given 0.077mg/20g atomization inhalation furosemide. Took out the plasma and pulmonary tissue at 0, 10, 20, 30, . 45, 60, 90, 120, 180min respectively (n=8). The plasma and pulmonary tissue homogenate liquid were precipitated with acetonitrile, centrifuged and then got the supernatant to inject. The HP-1100 HPLC system was adopted, with Ex=275nm, Em=410nm as detected wavelength, acetonitrile-0.05%H3PO4 (65:35) as mobile phase. The flow rate was 1.0ml/min. Determined the drug concentrations in plasma and pulmonary tissue homogenate liquid of the healthy mice with different doses, worked out the pharmacokinetic parameters ofatomization inhalation furosemide with software DAS and analyzed the primary parameters statistically. Results: The minimum detection concentrations in plasma and pulmonary tissue homogenate liquid were both 0.02 g/ml. The standard curve was linear in the range 0.02-1.5 g/ml. The average extraction recovery was more than 90%. The intra-day and inter-day RSD% were all less than 15%. In plasma and pulmonary tissue homogenate liquid of low-dose group, the average t1/2ka were 18.27 + 3.28 and 20.20 ?4.08min, the average t1/2 were 16.60 ?.52min and 24.62 ?7.69min,the average t1/2 were 26.88 + 8.02min 55.54 +16.83min, the Cmax were 0.54 + 0.19 g/ml and 0.29 + 0.02 g/ml . However, in plasma and pulmonary tissue homogenate liquid of high-dose group, the average t1/2ka were 18.04 + l.71min and20.46 ?4.59min, the average t1/2 were 11.78 + 3.83min and 23.96 + 6.13 min,the average t1/2 were 24.38 + 3.03min fP 48.46 + 14.62min, the Cmax were 0.73 + 0.06 g/ml and 0.62 + 0.05 g/ml. Conclusions: Constructed the determination method of furosemide in plasma and pulmonary tissue of mice. Determined the pharmacokinetic parameters of atomization inhalation furosemide in healthy mice. It had good relationship of the drug concentrations in plasma and pulmonary tissue homogenate liquid. The drug concentrations in plasma and pulmonary tissue distinctly increased with the dose's increase of atomization inhalation furosemide.