Objective:To establish a HPLC method for determination of 17997 in plasma,bile and tissue,and to study its
pharmacokinetics(PK)and
tissue distribution in rats after iv injection. Method: Doses of 4 or 1 mg . kg-1 were administrated to rats by iv injection. Blood,tissue and bile samples were collected in accordance with the experimental design. The drug levels in samples were measured by HPLC assay. The plasma protein binding rate was determined by equilibrium dialysis (ED) method using 0. 5 to 8 μg . mL-1 of 17997. Results: The main pharmacokinetic parameters of 17997 at dose of 4 mg . kg-1 in rats were as follows: T1/2β was 75. 71 min, C0 was 4. 51μg . mL-1 ,CL was 52. 5 mL . min-1.kg-1, AUC was 76. 16 min . μg . mL-1,respectively. The tissue concentration of 17997 in rats,at 15 min were 16. 55 μg . g-1 (lung) ,7. 34μg . g-1 (duodenum) ,6. 51 μg . g-1(liver),4. 18 μg . g-1(heart),3. 31 μg . g-1 (kidney) ,3. 12 μg . g-1 (spleen) ,1. 83 μg . g-1(thymus) and 0. 74 μg . g-1 (lymphnode) ,respectively. The accumulative excretions of 17997 in 24 hours in rat bile at doses of 4 and 1 mg . kg -1 were (55.4 ±9. 4)% and (58. 8±11. 8)% ,respectively. The binding rate of 17997 to rat plasma protein was high with a mean value of (92. 27 ±2. 91) % . Conclusion: We have successfully used the developed analytical method for 17997 to study its pharmacokinetical properties, distribution and excretion in rats after a rapid iv injection. The method was found to be sensitive, simple and rapid, suitable for application in preclinical and clinical pharmacokinetic studies. The distribution and excretion of 17997 in rats is fast. 17997 has the greatest affinity to lung,and high protein binding rate in rat plasma. 17997 was mainly excreted in bile.