Abstract
Sultamicillin tosilate (SBTPC), a new oral “mutual prodrug” of ampicillin (ABPC) combined with sulbactam (SBT) developed by Pfizer Co., was studied on its antibacterial activity in vitro, serum levels and urinary excretion of ABPC as well as those of SBT in humans after SBTPC administration. The effectiveness of the drug in patients was also examined. The results obtained were as follows:
1) Antibacterial activity in vitro: The bacteria isolated from clinical infection foci were examined on their sensitivity against SBTPC, ABPC, cefaclor (CCL) and cefalexin (CEX). SBTPC was found to be active against ABPC-resistant strains of S. aureus, Klebsiella, P. mirabilis and P. vulgaris. Even P. vulgaris strains highly resistant to CCL and CEX mostly showed considerable sensitivity to SBTPC.
2) Absorption and urinary excretion in humans: Cross-over studies on the serum levels and the urinary excretion of ABPC and SBT after single oral administration of SBTPC 750mg (equivalent to ABPC 440mg) were made in five healthy volunteers. The drug was given preprandially with or without an antacid (1g Sod. bicarbonate), or postprandially. The highest mean peak level in serum Was obtained by the postprandial administration (ABPC 5.42±1.02μg/ml, SBT 4.36±1.29μg/ml; 1 hr after dosage), followed by preprandial without antacid (ABPC 2.46±0.34, SBT 2.38±0.62; 2 hrs after) and that with antacid (ABPC 1.74±0.55, SBT 1.10±0.36; 3 hrs after)
No significant differences were found among the cumulative urinary excretion rates in six hours after those three regimens, although the urinary ABPC and SBT concentrations simulated the course of the serum levels
3) Clinical trials: Twenty-three patients with various infections (RTI 14, UTI 7, enteritis 2) were treated with SBTPC 750-1, 500mg/day for 3-14 days: Twenty of the cases well responded to the therapy; i.e.efficacy ratio was 87%.
As to the untoward reactions, one of the patients showed drug fever, two of them elavation of seral transaminases, and another slight anemia possibly attributable to the drug therapy.
These results suggest that sultamicillin is an oral antibacterial drug having usefulness at least comparable to those curretly used.
