Preliminary studies of offspring exposure to phenylbutazone and ivermectin during the perinatal period in a Holstein cow–calf model

Chamberlain, P; Fowler, Bruce A.; Sexton, Mary; Peggins, James O.; Bredow, J. von

doi:10.1016/s0041-008x(02)00074-1

Cited by 12 publications

(9 citation statements)

References 19 publications

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“…However, it is a drug that is characterized by a high molecular weight (874 Da) and size (Lo et al, 1985), properties which can limit its transplacental transfer to the fetus, as has been demonstrated by the results of the current study. These results agree with those reported by Chamberlain et al (2003) in pregnant cows, in which the administration of a therapeutic dose of ivermectin 5 days previous to parturition, resulted in very low plasma concentrations in the newborn calf, suggesting that the transfer of ivermectin through the bovine placenta is limited.…”

Section: Discussionsupporting

confidence: 92%

Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheep

Pérez

Palma

Núñez

et al. 2008

Vet Pharm & Therapeutics

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In pregnant sheep at 120-130 days of gestational age, a study was undertaken in order to characterize the pharmacokinetics and transplacental exchange of Ivermectin after maternal or fetal intravenous administration. Eight pregnant Suffolk Down sheep of 73.2 +/- 3.7 kg body weight (bw) were surgically prepared in order to insert polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. Following 48 h of recovery, the ewes were randomly assigned to two experimental groups. In group 1, (maternal injection) five ewes were treated with an intravenous bolus of 0.2 mg ivermectin/kg bw. In group 2, (fetal injection) three ewes were injected with an intravenous bolus of 1 mg of ivermectin to the fetus through a fetal femoral vein catheter. Maternal and fetal blood and amniotic fluid samples were taken before and after ivermectin administration for a period of 144 h post-treatment. Samples were analyzed by liquid chromatography (HPLC). A computerized non-compartmental pharmacokinetic analysis was performed and the results were compared by means of the Student t-test. The main pharmacokinetic changes observed in the maternal compartment were increases in the volume of distribution and in the half-life of elimination (t((1/2)beta)). A limited maternal-fetal transfer of ivermectin was evidenced by a low fetal Cmax (1.72 +/- 0.6 ng/mL) and AUC (89.1 +/- 11.4 ng.h/mL). While the fetal administration of ivermectin resulted in higher values of clearance (554.1 +/- 177.9 mL/kg) and lower values of t((1/2)beta) (8.0 +/- 1.4 h) and mean residence time (8.0 +/- 2.9 h) indicating that fetal-placental unit is highly efficient in eliminating the drug as well as limiting the transfer of ivermectin from the maternal to fetal compartment.

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Section: Discussionsupporting

confidence: 92%

Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheep

Pérez

Palma

Núñez

et al. 2008

Vet Pharm & Therapeutics

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“…This demonstrates a successful application of the Holstein cow–calf model to measure the transfer of ciprofloxacin from lactating mother to neonate. In contrast to previous studies of other drugs using this model, accumulation of ciprofloxacin in the calves (2.4×) did not result in plasma concentrations that would be considered toxic or even effective in the treatment of infections with susceptible organisms (Chamberlain, ). The milk concentrations of the drug were much higher than in the mothers' plasma, but still the calves received only a fraction of the mothers' dose (approximately 6%), and plasma concentrations in the calf were less than a quarter of the dams'.…”

Section: Discussioncontrasting

confidence: 89%

“…Although the cow–calf model is an animal model, the Holstein dairy cow and her own newborn calf demonstrate many similarities to the human mother nursing a newborn infant, which have been reviewed by Chamberlain et al . ().…”

Section: Introductionmentioning

confidence: 97%

“…Advanced animal models are therefore needed to provide milk and sufficient neonate plasma samples to fully describe the pharmacokinetics of the drug. One such model, described by Chamberlain et al ., ; uses the dairy cow and her own newborn calf. The relative size of this model provides a tenfold amplification of the human mother and infant.…”

Section: Introductionmentioning

confidence: 99%

“…Using the cow–calf model, it has been shown that phenylbutazone and ivermectin readily transfer into the milk of the treated cow, and when the calf is fed with the milk of her mother, the drug is well absorbed orally by the calf (Chamberlain, ). For both of these drugs, a small amount of the drug accumulated each time the calf consumed its mother's milk resulting in unexpectedly high concentrations of drug in the plasma of the calf after a week of nursing.…”

Section: Introductionmentioning

confidence: 99%

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A holstein cow–calf model for the transfer of ciprofloxacin through milk after a long‐term intravenous infusion

Chiesa

Idowu

Heller

et al. 2012

Vet Pharm & Therapeutics

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This study is part of an ongoing effort to develop animal models that provide milk and sufficient infant (offspring) plasma samples to fully describe a drug's pharmacokinetics to quantitate the risk to the nursing infant. Ciprofloxacin was administered to six healthy Holstein cows as a constant rate intravenous infusion (flow rate was weight adjusted) to achieve a steady-state concentration of approximately 300 ng/mL for 7 days. Plasma and milk samples were collected from the cow at regular intervals over the course of the 7 days. The plasma and milk samples were analyzed for ciprofloxacin by high-performance liquid chromatography. The milk was fed to calves, and calf plasma samples were analyzed to study the lactational transfer of ciprofloxacin from dam to nursing neonate. Remarkably, concentrations of ciprofloxacin in milk were 45 times higher than plasma drug concentrations in the dam. Approximately 6% of the administered dose was transferred to the milk, resulting in an average oral dose of 0.5 mg/kg to the calves with every feeding. The drug did not accumulate in the calves, and plasma concentrations were between one-tenth and one-fifth the plasma concentrations of the dam.

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Pain management for farm animals

Lin

2014

Farm Animal Anesthesia

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Preliminary studies of offspring exposure to phenylbutazone and ivermectin during the perinatal period in a Holstein cow–calf model

Cited by 12 publications

References 19 publications

Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheep

Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheep

A holstein cow–calf model for the transfer of ciprofloxacin through milk after a long‐term intravenous infusion

Pain management for farm animals

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