Pharmacokinetics of sulbactam and ampicillin intravenously applied in combination to healthy volunteers and patients. Determination of the ratio of the two drugs in serum and in various tissues.

The pharmacokinetics of sulbactam, a new beta-lactamase inhibitor, and ampicillin were investigated in 9 healthy volunteers and 125 patients. The two drugs were administered intravenously in combination (Unacid). Each subject received 1 g sulbactam and 2 g ampicillin. The two drugs showed a similar pharmacokinetic profile in humans. Relevant pharmacokinetic parameters were calculated using a 2-compartment model on the basis of the serum and urine concentrations determined in healthy volunteers. The ratio of sulbactam to ampicillin was found to be nearly constant (approx. 1:2), both in the blood, in several tissues and at various time points. The two compounds apparently penetrated well into the myometrium, renal cortex and medulla, the gall bladder wall, the tonsils and the cutis of the skin. The sulbactam/ampicillin ratios in the bile ranged from 1:3 to 1:13 over 2 h after the infusion. The concentrations of the two compounds measured in the various fluids and tissues of the body reached levels which are effective against beta-lactamase producing bacteria. The similar pharmacokinetics of sulbactam and ampicillin in humans are considered an essential prerequisite for the therapeutic efficacy of such a combination product.