Effect of the formulation on the bioequivalence of sultamicillin: tablets and suspension.
Sultamicillin (CAS 76497-13-7) is a pro-drug of a combination of ampicillin and sulbactam linked as a double ester. The aim of the present studies, performed in two different groups of volunteers, was to compare the bioavailability of 750 mg sultamicillin tablets (Duobaktam 750 mg tablets, study 1) and sultamicillin 250 mg/5mL suspensions (Duobaktam 250 mg/5mL, study 2). Each study was conducted according to an open, randomized, single-dose, two-period cross-over design in 24 healthy volunteers with a wash-out period from 7 to 14 days. Blood samples were taken up to 12 h post dosing, and concentrations of ampicillin and sulbactam were determined by a HPLC-UV method. In the first study, the 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of ampicillin and sulbactam were between 1.01-1.18 and 0.95-1.09 (AUC0-t) as well as between 0.87-1.04 and 0.80-0.96 (Cmax), respectively, and thus within the acceptance ranges. The 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of sultamicillin suspensions (2nd study) were between 0.94-1.16 (ampicillin) and 0.92-1.14 (sulbactam) for AUC0-t and between 0.96-1.23 (ampicillin) and 0.97-1.24 (sulbactam) for Cmax. These values were also within the acceptance range for bioequivalence studies. Concerning the secondary parameter tmax the 90%-confidence interval for the intra-individual differences for both ampicillin and sulbactam were between 0.00-0.50 in the first and between -0.17-0.00 in the second study, respectively. In the light of the present studies it can be concluded that the sultamicillin test formulations, i.e. tablet and suspension are bioequivalent to the respective reference formulations.
Koytchev
Rossen
R
Cooperative Clinical Drug Research and Development, Neuenhagen, Germany. mail@ccdrdag.com
Ozalp
Yildiz
Y
Erenmemisoglu
Aydin
A
Kunter
Ulrich
U
Alpan
Recep Serdar
RS
D000293:Adolescent; D000328:Adult; D000667:Ampicillin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D013407:Sulbactam / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013535:Suspensions; D013607:Tablets; D013810:Therapeutic Equivalency
D013535:Suspensions; D013607:Tablets; C035444:sultamicillin; D000667:Ampicillin; D013407:Sulbactam