Pharmacokinetics of ceftriaxone following single ascending intravenous doses in sheep

Abstract

The objective of this study was to evaluate the pharmacokinetics of CTX following intravenous administration of ascending doses in sheep. In this study, six clinically healthy Akkaraman sheep (2.4 ± 0.4 years and 50 ± 3 kg of body weight) were used. CTX was administered intravenously to each sheep at 20, 40, and 80 mg/kg doses in a crossover design with a 15-day washout period. Plasma concentrations of CTX were measured using the high-performance liquid chromatography-UV method. Pharmacokinetic parameters were calculated by non-compartmental analysis. CTX was well tolerated following administration at 20, 40, and 80 mg/kg doses. The elimination half-life following administration of 40 and 80 mg/kg doses were significantly longer than that of 20 mg/kg dose (P < 0.05). The volume of distribution at steady state was similar among the groups (P > 0.05). When compared to 20 mg/kg, dose-normalized AUC0–∞ at the 80 mg/kg dose significantly increased (P < 0.05). The relation between dose and AUC0–∞ was linear. Our study showed that CTX can be used at 12-h intervals for 20, 40, and 80 mg/kg doses to maintain T > minimum inhibitory concentration (MIC) of >40% for the treatment of infections caused by bacteria with MIC values ≤2, ≤4, and ≤16 μg/mL, respectively. This information may be helpful in adjusting the dosage regimen, but there is a need for future work.