Abstract: In this study,the toxicity test of azithromycin (AZM) was repeated to study the toxicokinetic characteristics and accumulation of the drug in SD rats after 1 month oral administration.Rats were given 300,120,and 50 mg/kg of AZM for 30 consecutive days.Blood was collected at different time points after the first and last doses.Roxithromycin was used as the internal standard.LC-MS/MS was used to determine the content of AZM in rat plasma,and DAS3.0 software was used to fit the toxicokinetic parameters.The results showed that the values of AUC_0-t of SD rats in the high,medium and low dose groups after the first administration were 176,67 and 35 mg·h/L;the values of average of AUC_0-∞ were 224,73 and 38 mg·h/L;the values of average t_1/2z were 35,18,and 19 h,respectively;the average C_max values were 11.7,5.6,and 2.8 mg/L,respectively;The average AUC_0-t values of SD rats in the high,medium and low dose groups after the last administration were 565,215 and 126 mg·h/L,respectively;the average AUC_0-∞ values were 1 511,454 and 213 mg·h/L,respectively;The average t_1/2z values were 108,71,and 59 h,respectively;the average C_max values were 14.2,7.9,and 6.1 mg/L,respectively.It is suggested that the toxicokinetics of AZM in SD rats presents linear kinetic characteristics,and there is no gender difference.Its toxicity is related to drug accumulation.

Key words: azithromycin, toxicokinetics, LC-MS/MS