Transplacental exchange of moxidectin after maternal or fetal intravenous administration in sheep

Abstract

The transplacental exchange of moxidectin after maternal or fetal intravenous (i.v.) administration was studied using the chronically catheterized fetal sheep model. Nine pregnant Suffolk Down sheep of 65.7 +/- 5.9 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 (maternal injection) five ewes were treated with an i.v. bolus of 0.2 mg of moxidectin/kg bw. In group 2, (fetal injection) an i.v. bolus of 1 mg of moxidectin was administered to the four fetuses by femoral vein catheters. Maternal and fetal blood and amniotic fluid samples were taken before and after moxidectin administration for a 144 h post-treatment period. Samples were analyzed by liquid chromatography. A noncompartmental pharmacokinetic analysis was performed and statistical differences were determined by mean of parametric and nonparametric statistical tests. Pharmacokinetic differences observed in maternal variables were shorter elimination half-life and mean residence time compared with values previously reported for ivermectin. Drug diffusion from maternal to fetal circulation (AUC(0-t) = 232.6 +/- 72.5 ng.h/mL) was statistically not different (P = 0.09) compared with fetal to maternal diffusion (AUC(0-t) = 158.0 +/- 21.6 ng.h/mL). Fetuses showed significantly (P = 0.008) lower drug body clearance values compared with those observed in the maternal side. Considering the observed transplacental passages between materno-fetal or feto-maternal circulations, we conclude that the placental barrier is not effective in preventing the moxidectin diffusion between mother and fetus.

Determination of Moxidectin in Serum by Liquid Chromatography-Tandem Mass Spectrometry and Its Application in Pharmacokinetic Study in Lambs

“…Regarding the sample preparation, most procedures described for MOX residue quantitation in plasma involve clean up steps using solid phase microextraction cartridges (SPME) 8,[11][12][13] and derivatization step. According to literature, the pharmacokinetic (PK) parameters of a veterinary drug vary according to the applied dose, animal species, type of animal and the application site, among others.…”

“…2, 2017 step. [8][9][10][11][12][13] Rarely are described analytical methods by using mass spectrometry as a detector for MOX.14 However, it is important to emphasize that analytical methods based on liquid chromatography coupled to mass spectrometry (HPLC-MS) are sufficiently sensitive and selective to quantify the compounds in very low amounts, not being necessary a derivatization step.Regarding the sample preparation, most procedures described for MOX residue quantitation in plasma involve clean up steps using solid phase microextraction cartridges (SPME) 8,11-13 and derivatization step. According to literature, the pharmacokinetic (PK) parameters of a veterinary drug vary according to the applied dose, animal species, type of animal and the application site, among others.…”

“…2, 2017 step. [8][9][10][11][12][13] Rarely are described analytical methods by using mass spectrometry as a detector for MOX.…”

Plasma disposition kinetics of moxidectin after subcutaneous administration to pregnant sheep

“…When combining this knowledge with the fact that these enzymes can be increased in the maternal and fetal livers as well as the placenta (Tracy et al ., ), the values of the reduced elimination half‐life observed in pregnant sheep of the current study could be due to a higher level of metabolism compared to those observed in adult nonpregnant sheep. Consequently, three unidentified metabolites of MXD were found in plasma of pregnant sheep, similar to those previously reported in cows (Lanusse et al ., ) and pregnant sheep (Pérez et al ., ). Although these analytes were observed in the plasma of the control group, they were less intense as chromatographic peaks.…”

“…Drug‐free plasma samples (1 mL) were fortified with MXD to reach the following final concentrations: 0.1, 0.5, 1.0, 5.0, 10.0, 25.0, and 50.0 ng/mL. Fortified and experimental plasma samples were vortexed vigorously for 30 sec; after 15 min of incubation at room temperature, an SPE procedure was performed according to our previous procedures (Pérez et al ., ). After SPE, the eluate was evaporated to dryness under a gentle stream of nitrogen at 60 °C in a water bath.…”