The irreversible beta-lactamase inhibitor sulbactam has been combined chemically via ester linkages with ampicillin to form sultamicillin . Upon oral absorption, sultamicillin is completely hydrolyzed to equimolar proportions of sulbactam and ampicillin, thereby acting as an efficient mutual prodrug. In rats, sultamicillin delivered 2 to 2.5 times greater total bioavailability for ampicillin and sulbactam than when each was used individually. Actual plasma or serum concentrations (measured in micrograms per milliliter) of ampicillin and sulbactam produced by sultamicillin were generally equivalent in rats, mice, and beagle dogs. Further studies also indicated that the components of sultamicillin were widely distributed in the various tissues of rats. These findings suggest that sultamicillin might be an effective agent against a variety of infections produced by both beta-lactamase-resistant and beta-lactamase-susceptible microorganisms.