Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to neonatal calves

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination after intravenous (i.v.) and intramuscular (i.m.) injection at a single dose rate of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were studied in 10-day-old neonatal calves (n = 10). The plasma concentration-time data of both antibiotics were best fitted to an open two-compartment model after i.v. administration. After i.m. administration, an open two-compartment model demonstrated first order absorption. The apparent volumes of distribution of ampicillin and sulbactam, calculated by the area method, were 0.20 +/- 0.01 and 0.18 +/- 0.01 L/kg, respectively, and the total body clearances were 0.51 +/- 0.03 and 0.21 +/- 0.01 L/kg h. The elimination half-lives of ampicillin after i.v. and i.m. administration were 0.99 +/- 0.03 and 1.01 +/- 0.02 h, respectively, whereas for sulbactam the half-lives were 2.24 +/- 0.02 and 3.44 +/- 0.94 h. The bioavailability after i.m. injection was high and similar for both drugs (70.31 +/- 0.2% for ampicillin and 68.62 +/- 4.44% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.47 +/- 0.02 and 0.72 +/- 0.01 h, respectively) and peak concentrations were also similar but not proportional to the dose administered (17.88 +/- 0.91 mg/L of ampicillin and 12.92 +/- 0.79 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after i.m. administration. Since the plasma concentrations of sulbactam were consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a ratio higher than 2:1. (c) 2004 Elsevier Ltd. All rights reserved.