title: Pharmacokinetics of an ampicillin/sulbactam (2:1) combination in rabbits.
abstract: The pharmacokinetics of a 2:1 ampicillin-sulbactam combination in six rabbits, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were investigated by using a high performance liquid chromatographic method for determining plasma concentrations. The plasma concentration-time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The disposition curves for both drugs were best described by an open two-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method for ampicillin and sulbactam were 0.62 +/- 0.09 and 0.45 +/- 0.05 L/kg, respectively, and the total body clearances were 0.65 +/- 0.04 and 0.42 +/- 0.05 L/kg h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.64 +/- 0.11 and 0.63 +/- 0.16 h, respectively, whereas for sulbactam the half-lives were 0.74 +/- 0.12 and 0.77 +/- 0.17 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (73.34 +/- 10.08% for ampicillin and 83.20 +/- 7.41% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.20 +/- 0.09 and 0.34 +/- 0.15 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.07 +/- 3.64 mg/L of ampicillin and 8.42 +/- 1.74 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after intramuscular administration in rabbits.
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Murcia, Campus de Espinardo, 30.071-Murcia, Spain. escudero@um.es
authors.forename: E
authors.initials: E
authors.lastname: Escudero
authors.forename: M S
authors.initials: MS
authors.lastname: Vicente
authors.forename: J M
authors.initials: JM
authors.lastname: Serrano
authors.forename: C M
authors.initials: CM
authors.lastname: Cárceles
mesh_terms: D000327:Adsorption; D000667:Ampicillin / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D004359:Drug Therapy, Combination / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D011817:Rabbits; D013407:Sulbactam / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: C035444:sultamicillin; D000667:Ampicillin; D013407:Sulbactam