Objective To study the pharmacokinetics of HMS-01 in rats and provide support for subsequent study. Methods A sensitive and specific method for the determination of HMS-01 in plasma and other biological samples was established by LC-MS/MS. The pharmacokinetics of HMS-01 in rats was studied by the established method. The pharmacokinetics of one dose of single intragastric administration and one dose of single intravenous administration in SD rats were studied, and the basic pharmacokinetic parameters were obtained. Results After intravenous injection of 1 mg/kg HMS-01, the area under the plasma concentration-time curve AUC_0-t of male and female rats was 221 ng·h/ml and 409 ng·h/ml, respectively. The average clearance rates were 4.53 L/h·kg and 2.41 L/h·kg, respectively. The average plasma elimination half-lives were 0.786 h and 1.27 h, and the apparent distribution volume was 5.13 L/kg and 3.82 L/kg, respectively. After intragastric administration of 30 mg/kg HMS-01, the peak time of plasma concentration in rats was 1.17 h, the peak concentration of C_max was 1 243 ng/ml, and the elimination half-life t_1/2 was 2.00 h. The AUC_0-t of male and female rats was 2 271 and 8 529 ng·h/ml respectively, and their bioavailability was 34.3% and 69.5% respectively. Conclusion The pharmacokinetics of HMS-01 in rats has significant gender differences. It is well absorbed orally, and the bioavailability of HMS-01 in females is much higher than that in males.

Objective To establish a rat model of chronic atrophic gastritis and explore the factors inducing atrophy.Methods In accordance with repeated orthogonal design of L8(27), 60% alcohol and 20mmol/L sodium deoxycholate (served as factor A), 0.05%-0.1% ammonia water (factor B), 0.05% indomethacin (factor C) were given, alone or in combination, to rats in three experiments for 3 months, 6 months or 9 months respectively. Then the rats were dissected, and their pathologic changes of the gastric mucosa were assessed.Results Typical signs of chronic atrophic gastritis (CAG) were found in all rats which were treated with factor A, B, C alone or in combination for 6 or 9 months. No significant difference of pathologic changes of gastric mucosa was found between the rats treated for 6 months and those for 9 months. No obvious CAG signs were found in the rats treated with factor A, B, C for 3 months.Conclusion Sixty percent of alcohol, 20mmol/L sodium deoxycholate, 0.05%-0.1% ammonia water and 0.05% indomethacin given to Sprague-Dawley rats for 6 months can successfully establish the animal model of CAG. Prolongation of the model-establishment time is not able to further facilitate the atrophy of gastric mucosa.