Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheep

J Vet Pharmacol Ther. 2008 Oct;31(5):406-14. doi: 10.1111/j.1365-2885.2008.00971.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparasitic Agents / administration & dosage
  • Antiparasitic Agents / blood
  • Antiparasitic Agents / pharmacokinetics*
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Female
  • Fetal Blood / chemistry
  • Fetus / metabolism*
  • Half-Life
  • Injections, Intravenous
  • Ivermectin / administration & dosage
  • Ivermectin / blood
  • Ivermectin / pharmacokinetics*
  • Maternal-Fetal Exchange
  • Metabolic Clearance Rate
  • Pregnancy
  • Pregnancy, Animal / metabolism*
  • Sheep

Substances

  • Antiparasitic Agents
  • Ivermectin