Pharmacokinetics and bioavailability of sultamicillin estimated by high performance liquid chromatography

Abstract

Sultamicillin is an orally absorbed double ester of sulbactam (penicillanic acid sulphone, a semisynthetic inhibitor of the η-lactamases of many Gram-positive and Gram-negative species) and ampicillin. First-pass hydrolysis of this prodrug liberates equimolar proportions of sulbactam and ampicillin into the systemic circulation. An HPLC assay for sulbactam in plasma, saliva and urine is described and was used to determine the absolute bioavailability of sulbactam and ampicillin from sultamicillin in six normal male volunteers who each received a single 750 mg oral dose of sultamicillin or an iv dose of the equivalent amounts of ampicillin (441 mg) and sulbactam (294 mg). Treatments were given in random order with not less than four days intervening. The mean peak plasma concentrations and time to peak of sulbactam and ampicillin following the 750 mg oral dose of sultamicillin were 8–9 and 91 mg/1 and 0–96 and 0–92 h respectively. The half lives, systemic and renal clearances for sulbactam and ampicillin were similar. The bioavailability for both drugs from sultamicillin as estimated from both plasma and urine pharmacokinetics was better than 80%. We conclude that sultamicillin is an extremely efficient prodrug for ampicillin and sulbactam and that the HPLC assay method is accurate, rapid and easier to perform than the differential microbiological assay.