Bio equivalence Study of Sultamicillin Suspensions

Abstract

Sultamicillin (CAS 76497-13-7) is a prodrug combination of ampicillin (CAS 69-53-4) and sulbactam (CAS 68373-14-8), with the antibiotic ampicillin and the beta-lac-tamase inhibitor sulbactam chemically linked as double ester. The present study was performed to investigate the relative bioavailability and to assess the bioequivalence of two different sultamicillin suspensions (Devasid^© 250 mg/5 ml as test preparation and 375 mg/7.5 ml of the originator product as reference preparation). Twenty-four healthy male volunteers received equal doses of the sultamicillin preparations according to an open, randomised, single-dose, two-period cross-over design with a wash-out phase of 7 days.

Blood samples for pharmacokinetic profiling were taken up to 8 h post-dose, and ampicillin and sulbactam plasma concentrations were determined with a validated LC-MS/MS method.

Maximum plasma concentrations (C_max) of 11,267.4 ng/ml (ampicillin, test), 10,864.4 ng/ml (ampicillin, reference), ng/ml (sulbactam, test and ng/ml (sulbactam, reference) were achieved. Areas under the plasma concentration-time curve (AUC_0→∞)of 17,512.9 ng · h/ml (ampicillin, test), 18,388.0 ng · h/ml (ampicillin, reference), 10,971.7 ng · h/ml (sulbactam, test) and 11,181.2 ng · h/ml (sulbactam, reference) were calculated. The median t_max was 0.69 h (ampicillin, test), 0.85 h (ampicillin, reference), 0.72 h (sulbactam, Devasid^©) and 0.83 h (sulbactam, reference). Plasma elimination half-lives (t_1/2) of 1.04 h (ampicillin, test), 1.03 h (ampicillin, reference), 1.26 h (sulbactam, Devasid^©) and 1.00 h (sulbactam, reference) were determined. Both primary target parameters AUC_0→∞ and C_max of ampicillin and sulbactam were tested parametrically by analysis of variance (ANOVA) and the 90% confidence intervals were between 84.58%-117.80% (AUC_0→∞ ampicillin), 92.37%-l 19.93% (C_max, ampicillin), 85.81 %-l 20.50% (AUC_0→∞, sulbactam) and 88.41 %-117.57% (C_max, sulbactam). Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and C_max the 90% confidence intervals of the T/R-ra-tios of logarithmically transformed data were in the generally accepted range of 80%-125%.

Key words

Ampicillin - Antibiotics - CAS 69-53-4 - CAS 68373-14-8 - CAS 76497-13-7 - Devasid© - Sulbactam - Sultamicillin, bioequivalence, pharmacokinetics, suspension