Pharmacokinetics of ticarcillin and ticarcillin-probenecid in sheep

Serum concentrations of ticarcillin were measured serially over a period of 12h in a cross over trial involving 6 healthy adult ewes after intravenous and intramuscular (IM) administration of 40 mg ticarcillin per kg body weight. Probenecid (40 mg/kg) was also administered IM immediately before the IM administration of 40 mg/kg ticarcillin. Pharmacokinetic values after intravenous administration were: half-life of elimination (T 1/2 beta) = 0.90 +/- 0.09 h; volume of distribution at steady state (Vdss) = 456.8 +/- 106.6 ml/kg, total body clearance (CIB) = 614.5 +/- 81.2 ml/h/kg. Ticarcillin persisted in serum at greater than or equal to 1.5 micrograms/ml for 4 hours. Pharmacokinetic and bioavailability values after intramuscular administration were: half-life of absorption (T 1/2 ab) = 8.08 +/- 1.98 min; T 1/2 beta = 0.96 +/- 0.07 h. Peak serum concentration (Cmax) was 31.11 +/- 6.02 micrograms/ml at 0.50 h (Tmax), bioavailability (F) was 0.82 +/- 0.09. After ticarcillin was administered IM together with probenecid the T 1/2 ab was 33.9 +/- 13.7 min, the T 1/2 beta 2.66 +/- 0.65 h, Cmax = 44.87 +/- 5.58 at 1.33 +/- 0.44 h, and F = 1.25 +/- 0.23.