Comparative plasma pharmacokinetics and tolerance of florfenicol following intramuscular and intravenous administration to camels, sheep and goats

摘要

Florfenicol, a monofluorinated analogue of thiamphenicol, has a broad antibacterial spectrum. The pharmacokinetics of florfenicol was studied following a single intravenous (i.v.) or intramuscular (i.m.) injection at a dose of 20 mg/kg body weight in healthy male camels, sheep and goats. The concentration of florfenicol in plasma was determined using a microbiological assay. Pharmacokinetic analysis was performed using a two-compartment open model. Following i.m. administration, the maximum plasma concentration of florfenicol (C-max) reached in camels, sheep and goats was 0.84+/-0.08, 1.04+/-0.10 and 1.21+/-0.10 mug/ml, respectively, the the time required to reach C-max (t(max)) in the same three respective species was 1.51 +/- 0.14, 1.44 +/- 0.10 and 1.21 +/- 0.10 h. The terminal half-life (t(1/2beta)) and the fraction of the drug absorbed (F%) in camels, sheep and goats were 151.3 +/- 16.33, 137.0 +/- 12.16 and 127.4 +/- 11.0 min, and 69.20% +/- 7.8%, 65.82% +/- 6.7% and 60.88% +/- 5.9%, respectively. The MRT in the same three respective species was 4.01 +/- 0.45, 3.42 +/- 0.39 and 2.98 +/- 0.32 h. Following i.v. administration, the terminal half-life (t(1/2beta)) and total body clearance (Cl-B) in camels, sheep and goats were 89.5 +/- 9.2, 78.8 +/- 8.3 and 71.1 +/- 8.9 min and 0.33 +/- 0.04, 0.30 +/- 0.03 and 0.27 +/- 0.03 L/h per kg, respectively. The area under the curve (AUC(0) (infinity)) and the mean residence time (MRT) in the same three respective species were 60.61 +/- 6.98, 62.45 +/- 6.56 and 74.07 +/- 7.85 mug/ml per h, and 2.71 +/- 0.31, 2.34 +/- 0.25 and 2.11 +/- 0.23 h. These data suggest that sheep and goats absorb and clear florfenicol to a broadly similar extent, but the rate and extent of absorption of the drug tends to be higher in camels. Drug treatment caused no clinically overt adverse effects. Plasma enzyme activities and metabolites indicative of hepatic and renal functions measured 1, 2, 4 and 7 days following the drug treatment were within the normal range, indicating that the drug is safe at the dose used.