Abstract :
In pregnant sheep at 120–128 days of gestational age, a study was done to evaluate the
effect of the co-administration of verapamil (Vpm) and ivermectin (IVM) on the maternal
and fetal disposition kinetics after intravenous administration of IVM. Ten pregnant
Suffolk Down sheep of 63.5±6.6 kg body weight (bw) were surgically prepared to insert
polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. The ewes were
randomly assigned to two experimental groups. In Group 1 (control), 5 ewes were treated
with an intravenous bolus of 0.2mg IVM/kg bw. In Group 2 (Vpm-IVM), 5 ewes were subcutaneously
treated with Vpm (2.5 mg/kg×3 doses at 12 h intervals) and 0.2 mg/kg IVM
by intravenous route. Maternal and fetal blood samples were taken before and after IVM
administration during a 144 h post-treatment period. Samples were analyzed by liquid
chromatography (HPLC). A non-compartmental pharmacokinetic analysis was performed
and statistical differences were determined using the Mann–Whitney U-test.
Significantly higher IVM levels in maternal plasma concentrations were determined after
co-administration of Vpm/IVM compared with the group treated with IVM alone. Significant
decreases in the volume of distribution and in the half-life of elimination (t½ˇ) were
observed in the Vpm/IVM treated group. A significantly faster (Tmax) and higher (Cmax)
(P < 0.05) increase in IVM fetal plasma concentrations were observed in the group of fetuses
from pregnant ewes treated with Vpm/IVM. The results of our study support the hypothesis
that pharmacological blockage of P-glycoprotein with Vpm can increase the transfer of IVM
to fetal circulation.
