Pharmacokinetics and pharmacodynamics of two in-feed chlortetracycline regimens provided to beef cattle

Abstract

Plasma chlortetracycline (CTC) concentration data were subjected to Monte Carlo simulation of area under the concentration curve (AUC) values related to bovine respiratory disease pathogen MIC distributions to evaluate target attainment rates. Crossbred Hereford heifers were randomly assigned into two treatment groups. Treatment group (A) received chlortetracycline (CTC) at a target dose of 22 mg/kg of bodyweight daily for 5 consecutive days (n = 8) and group (B) received CTC at 350 mg/head per day (1.5 ± 0.2 mg/kg based on actual bodyweights) for seven consecutive days (n = 8). Non-compartmental analysis was used to calculate plasma-free drug CTC area under the concentration curves. The mean observed (±SD) free drug AUC values were 4.18 (±1.72) μg × h/mL and 0.30 (±0.06) μg × h/mL for treatment groups A and B, respectively. The probability of target attainment for AUC₂₄/MIC values of 25 and 12.5 was modeled using Monte Carlo simulations. Treatment group A achieved >90% target attainment (AUC₂₄/MIC of 25) at an MIC of 0.06 μg/mL, whereas treatment group B displayed only 12.6% target attainment (AUC₂₄/MIC of 12.5) at the lowest MIC evaluated (0.015 μg/mL). Both in-feed CTC regimens failed to obtain a reasonable target attainment rate in light of expected MIC distributions of potential pathogens.