Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheep.
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.
Pérez
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R
Laboratorio de Farmacología, Departamento de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad de Concepción, Chillán, Chile. rubperez@udec.cl
Palma
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Núñez
M J
MJ
Cox
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J
D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000378:metabolism*; D006207:Half-Life; D007275:Injections, Intravenous; D007559:Ivermectin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008431:Maternal-Fetal Exchange; D008657:Metabolic Clearance Rate; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D012756:Sheep
D000977:Antiparasitic Agents; D007559:Ivermectin