Pharmacokinetics of tulathromycin in pregnant ewes (Ovis aries) challenged with Campylobacter jejuni

Abstract

The purpose of this study was to evaluate the pharmacokinetics of tulathromycin in the plasma and maternal and fetal tissues of pregnant ewes when administered within 24 hours of a single, IV Campylobacter jejuni (C. jejuni) challenge. Twelve, pregnant ewes between 72–92 days of gestation were challenged IV with C. jejuni IA3902 and then treated with 1.1 ml/45.36 kg of tulathromycin subcutaneously 18 hours post-challenge. Ewes were bled at predetermined time points and euthanized either at a predetermined time point or following the observation of vaginal bleeding or abortion. Following euthanasia, tissues were collected for bacterial culture, pharmacokinetics and histologic examination. The maximum (geometric) mean tulathromycin plasma concentration was estimated at 0.302 μg/mL, with a peak level observed at around 1.2 hours. The apparent systemic clearance of tulathromycin was estimated at 16.6 L/h (or 0.28 L/kg/h) with an elimination half-life estimated at approximately 22 hours. The mean tissue concentrations were highest in the uterus (2.464 μg/g) and placentome (0.484 μg/g), and were lowest in fetal liver (0.11 μg/g) and fetal lung (0.03 μg/g). Compared to previous reports, results of this study demonstrate that prior IV administration of C. jejuni appeared to substantially alter the pharmacokinetics of tulathromycin, reducing both the peak plasma concentrations and elimination half-life. However, additional controlled trials are required to confirm those observations.

Comparisons of plasma and fecal pharmacokinetics of danofloxacin and enrofloxacin in healthy and Mannheimia haemolytica infected calves

“…A commercial software, PKanalix (PKanalix, Monolix Suite 2019R1, Lixoft, France) 25 , was used to compute PK parameters using a statistical moments approach, which included area under the plasma/fecal concentration versus time curve extrapolated to infinity (AUC inf ), area under the plasma/fecal concentration versus time curve from dosing to the last sampling time point (AUC 0~48 ), area under the plasma/fecal concentration versus time curve from the time of dosing to the last measurable positive concentration (AUC last ), area under the first moment curve extrapolated to infinity (AUMC inf ), area under the first moment curve from dosing to the last measurable concentration (AUMC last ), apparent clearance (CL/F), maximum observed drug concentration (C max ), mean residence time from the time of dosing to the last measurable concentration (MRT last ), time to the maximum concentration (T max ), elimination/terminal half-life (T 1/2 λz), elimination rate (λz), and apparent volume of distribution associated with the terminal phase (Vz/F). Using the non-compartmental analysis (NCA), the log-linear trapezoidal method was used to calculate AUC in PKanalix.…”