Abstract: In this study, 9 aztreonam prodrug compounds were designed and synthesized, and their metabolic stability in plasmas of different species (rat, mouse, dog, monkey and human) were evaluated. Species differences were observed in aztreonam carboxylates's sensitivity to the plasma esterases among different species, and the hydrolysis rates of aztreonam carboxylates in rodent plasmas were much higher than in non-rodent plasmas. Moreover, the hydrolysis rates of aztreonam carboxylates might be positively correlated with the ClogP values in human plasma. These results provide useful guidance for the further development of monocyclic β lactam prodrugs.