title: Bioequivalence 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-lactamase 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), 6,360.6 ng/ml (sulbactam, test and 6,410.7 ng/ml (sulbactam, reference) were achieved. Areas under the plasma concentration-time curve (AUC(0-infinity) of 17,512.9 ng x h/ml (ampicillin, test), 18,388.0 ng x h/ml (ampicillin, reference), 10,971.7 ng ng x h/ml (sulbactam, test) and 11,181.2 ng x 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-infinity) 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-infinity), ampicillin), 92.37%-119.93% (C(max), ampicillin), 85.81%-120.50% (AUC(0-infinity), 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-ratios of logarithmically transformed data were in the generally accepted range of 80%-125%.
authors.affiliation: Pharmakin GmbH, Gesellschaft für Pharmakokinetik, Ulm, Germany. reinhard.sailer@pharmakin.de
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sailer
authors.forename: Peter
authors.initials: P
authors.lastname: Arnold
authors.forename: Aydin
authors.initials: A
authors.lastname: Erenmemişoğlu
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Martin
authors.forename: Uygur
authors.initials: U
authors.lastname: Tamur
authors.forename: Ilker
authors.initials: I
authors.lastname: Kanzik
authors.forename: A Atilla
authors.initials: AA
authors.lastname: Hincal
mesh_terms: D000328:Adult; D000667:Ampicillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002138:Calibration; D018592:Cross-Over Studies; D006801:Humans; D008297:Male; D011786:Quality Control; D021241:Spectrometry, Mass, Electrospray Ionization; D013407:Sulbactam / Q000008:administration & dosage / Q000493:pharmacokinetics; D013535:Suspensions; D013810:Therapeutic Equivalency
chemical_list: D000900:Anti-Bacterial Agents; D013535:Suspensions; C035444:sultamicillin; D000667:Ampicillin; D013407:Sulbactam