Plasma pharmacokinetics of oral chlortetracycline in group fed, ruminating, Holstein steers in a feedlot setting.

ABSTRACT

Chlortetracycline HCl (CTC) has impacted profitable livestock production since 1945. However, pharmacokinetic parameters for CTC in ruminating cattle are unavailable in peer-reviewed literature. A total of 18 steers were randomized to 4.4, 11, or 22 mg/kg/day p.o. CTC treatment groups (n = 6). Chlortetracycline treatment was offered as one-half of the daily dose b.i.d. (160 total doses/group) for 80 days. Blood samples were collected at selected time points throughout an 83-day study and analyzed with a solid phase extraction technique and novel ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy analytical method. Noncompartmental analysis (NCA) determined individual pharmacokinetic parameters by treatment group with coefficient of variation (CV %) estimates. A one-compartment open model with first order absorption and elimination, where absorption rate constant was equal to elimination rate constant, was fitted using nonlinear mixed effects modeling (NLMEM). NLMEM determined the primary pharmacokinetic parameters volume of distribution (V/F, 40.9 L/kg) and rate constant (k, 0.0478 h(-1)), and the secondary parameters dose-normalized area under the curve (AUC/D, 0.29 h x microg/L), clearance (Cl/F, 1.8 L/kg/h), elimination half-life (t(1/2), 16.2 h), C(max/Dose) (4.5 ng/mL), and time of C(max) (T(max), 23.3 h) with improved CV estimates over NCA. Dose linearity was confirmed by anova of parameters derived from NCA by treatment group. Further studies are necessary for determining absolute bioavailability and pharmacokinetic-pharmacodynamic relationships of CTC in group fed, ruminating cattle.