Disposition and bioavailability of neomycin in Holstein calves

The disposition and absorption kinetics of neomycin were studied in healthy ruminating dairy calves (n = 6), approximately 3-months-old. The calves were treated with single intravenous (i.v.) (12 mg/kg), intramuscular (i.m.) (24 mg/kg), oral (p.o.) (96 mg/kg) and repeated p.o. (96 mg/kg, b.i.d., 15 1/2 days) doses of neomycin. A 3-week rest period was allowed between treatments A and B, and B and C. Baseline and serial venous blood samples were collected from each calf. Plasma concentrations of neomycin were determined by a high performance liquid chromatography procedure. The resulting data were evaluated by using compartmental pharmacokinetic models and nonlinear least squares regression analysis. The mean of some selected parameters were t1/2 lambda 3 7.48 +/- 2.02 h, Clt = 0.25 +/- 0.04 L/h/kg, Vd(ss) = 1.17 +/- 0.23 L/kg, and MRT = 4.63 +/- 0.87 h for the i.v. data and t1/2 = 11.5 +/- 3.8 h, MRTabs = 0.960 +/- 1.001 h, F = 127 +/- 35.2%, and Clt/F = 0.199 +/- 0.047 L/h/kg for the i.m. data, respectively. Only one calf absorbed neomycin to any significant degree (F = 0.0042) after a single p.o. dose. Selected mean parameters determined after repeated oral dosing were: F = 0.45 +/- 0.45%, Cmax = 0.26 +/- 0.37 microgram/ml, and tmax = 2.6 +/- 2.9 h. Terminal half-lives determined for the i.v. and i.m. treatments were considerably longer than those reported previously in the literature.