Pharmacokinetics of chlortetracycline in maternal plasma and in fetal tissues following oral administration to pregnant ewes

Abstract

The purpose of this study was to determine if concentrations of chlortetracycline could be detected in fetal plasma or tissues after administering an oral dose of chlortetracycline (CTC; 500 mg/head/day) reported to be effective in controlling Campylobacter spp. abortions. Five pregnant ewes were administered 250 mg/head twice a day (total dose 500 mg/hd/d) for 7 days. On the beginning of day 7, intravenous catheters were surgically implanted or inserted into the fetus and dam. Plasma samples were collected from the ewe and fetus at various time points before and up to 36 hr after the last dose of CTC. All ewes were then sacrificed, and tissues were harvested from the fetus for drug analysis. Concentrations of CTC in maternal plasma were consistent with our previous study and below the minimum inhibitory concentration of Campylobacter abortion isolates. Concentrations of CTC were below the limit of detection in three of five fetal plasma samples and all of the placenta, amniotic fluid, and fetal stomach contents. Low concentrations were detectable in fetal kidney and liver, suggesting that CTC reaches the fetus, although at a variable and low ratio when compared to maternal concentrations.

Management of Coxiella burnetii infection in livestock populations and the associated zoonotic risk: A consensus statement

“…In vitro, C. burnetii is sensitive to several antimicrobial drugs, including tetracycline. In‐feed administration of antimicrobial drugs do not reach target concentrations in reproductive tissues or the fetus . In the face of an outbreak, treatment with two successive injections of oxytetracycline during the last month of pregnancy has been proposed for use in goats .…”

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

“…6 Area under the moment curve from time 0 to infinity. 7 Mean residence time. 8 Slope of the terminal (elimination) phase.…”

“…The only antibiotic approved to treat or prevent campylobacter abortion in sheep is chlortetracycline [5]. However, the vast majority of recent US C. jejuni isolates are reported to be resistant to tetracyclines (including chlortetracycline), and pharmacokinetic studies have shown that feeding chlortetracycline to sheep at the approved dose (80 mg/head/day), or at an even higher, unapproved dose (500 mg/head/day), resulted in levels that were presumed to be subtherapeutic in pregnant ewe plasma and largely undetectable in fetal tissues and amniotic fluid [1,[6][7][8][9]. Results of these studies indicate that feeding chlortetracycline is unlikely to provide therapeutic benefit during an outbreak of C. jejuni abortion in US flocks.…”

Pharmacokinetics of tulathromycin in fetal sheep and pregnant ewes

“…Catheters were surgically placed in the fetus using a previously described procedure (Washburn, Sawant, Lunde, Wu, & Cudd, 2013;Washburn et al, 2018). In brief, a ventral midline laparotomy was performed, the uterus was externalized and incised, and a fetal hindlimb was exteriorized.…”

“…Reports of resistance and lack of efficacy have prompted investigation of the pharmacokinetics of the common feed‐additive chlortetracycline. Feeding chlortetracycline to sheep at the approved dose and at the higher, unapproved dose results in subtherapeutic levels in pregnant ewe plasma and mostly undetectable levels in fetal tissues and amniotic fluid (Washburn et al., , ). Chlortetracycline in feed requires a veterinary feed directive, and extra‐label use or use of increased doses of feed additives is illegal in the United States.…”