Abstract
Ceftiofur is an important broad-spectrum 3rd generation cephalosporin antibiotic. Owing to its time-dependent antimicrobial actions, the length of time of being above bacterial MIC is the critical point in using ceftiofur for chemotherapy rather than its peak of concentration. Consequently, this experiment was carried out to evaluate, for the first time, the pharmacokinetics of the long-acting ceftiofur crystalline acid-free form (ceftiofur-CAF) in camels. Ceftiofur-CAF 200 mg/ml suspension sterile solution was injected i/m at a dose 6.6 mg/kg. Blood samples were collected from the jugular vein in vacutainer tubes at 0, 0.13, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, and 144 hours after administration of the drug. Ultrahigh Performance Liquid Chromatography-Mass Spectrometry (UPLC MS/MS) was used to measure serum concentration. Pharmacokinetic modeling was by a two-compartment model. Pharmacokinetics of ceftiofur-CAF after single i/m injection in she-camels was best modeled in the two-compartment model, where the drug slowly distributed to a second compartment with poor tissue penetration and high preference to the central compartment. In this study, the maximum plasma concentration (C-max) was 9.29 +/- 0.42 mu g/ml at T-max equals 9.41 +/- 1.35 h. The area under the curve (AUC(0-infinity)) was 354.1 +/- 57.22 mu g/ml*h. The distribution and elimination half-lives were 7.42 and 46.13 h, respectively. The mean residence time (MRT) was 42.01 h. Compared with the rapidly absorbed form of ceftiofur (ceftiofur-RAF) in camels, there was almost similar maximal serum concentration but with delayed time to maximal concentration (T-max), longer means residence time (MRT) and higher distribution and elimination half-lives. In terms of antibacterial efficacy, ceftiofur-CAF stayed above a previously recommended level of 0.2 mu g/ml for 7 days, which can be achieved after a single i/m injection of 6.6 mg/kg. The obtained pharmacokinetics data in camels recommends repeated administration of 2 days apart for bacteria requiring MIC levels above 2 mu g/ml.