Comparison of effects of albendazole sulfoxide on in vitro produced bovine embryos and rat embryos.

OBJECTIVE: To evaluate and compare effects of albendazole sulfoxide (ABZSO) on rat embryos and bovine embryos produced in vitro. ANIMALS: In vitro produced bovine embryos. Rat embryos recovered from naturally bred Sprague-Dawley rats. PROCEDURE: 4- and 8-cell bovine embryos were randomly allocated to ABZSO or vehicle control groups. After 48 hours, embryos were evaluated for cell number and blastomere morphology. Rat embryos of similar stages, flushed from the uterine tube on gestational day 2-5, were randomly allocated to treatment or control groups. After 24 hours, embryos were evaluated as described previously. RESULTS: 44% of control bovine embryos divided in culture (> or = 16-cell stage). Fifteen percent of the controls had morphologic abnormalities, including disparity in blastomere size and cytoplasmic vacuoles and stippling. Treated (> or = 1 microgram of ABZSO/ml) bovine embryos differed (P < 0.0001) from controls, with 4% development and 93% abnormal morphology. Forty-five percent of control rat embryos divided in culture. Treated (> or = 500 ng of ABZSO/ml) rat embryos differed (P < 0.0003) from controls with regard to ability to divide. There were no consistent morphologic abnormalities in rat embryos. CONCLUSIONS: In vitro produced bovine embryos were susceptible to ABZSO at a concentration > or = 1 microgram/ ml, resulting in decreased ability to divide and presence of gross morphologic abnormalities. Rat embryos produced in vivo and exposed in vitro to ABZSO at a concentration > or = 500 ng/ml had decreased ability to divide in culture. CLINICAL RELEVANCE: Despite severe effects of ABZSO (> or = 1 microgram/ml) on bovine embryo development in vitro, it is beyond the scope of this study to speculate whether a therapeutic dosage of albendazole (10 mg/kg of body weight) would result in necessary concentrations of ABZSO in vivo to disrupt embryogenesis.

Determination of concentration of albendazole sulfoxide in plasma and uterine fluid of heifers.

OBJECTIVES: To determine time and concentration of peak plasma and uterine fluid concentrations of albendazole (ABZ) sulfoxide (ABZSO) in heifers after oral administration of ABZ. SAMPLE POPULATION: 25 young Angus and Simmental heifers maintained on pasture with ad libitum access to hay and water. PROCEDURE: Heifers were assigned at random to ABZ or control (water) groups, and were drenched with ABZ suspension at a dosage of 15, 30, 60, or 120 mg/kg of body weight, or with water. Plasma was collected hourly, from 14 to 25 hours after administration of ABZ or water. After a drug-withdrawal period, heifers were synchronized for estrus and drenched with 60 mg of ABZ/kg, or water (50 ml). Each uterine horn was flushed. All samples were extracted and subjected to high-performance liquid chromatography analysis. RESULTS: For all groups, highest mean +/- SEM plasma concentration of ABZSO was observed between 15 and 16 hours after ABZ administration, at 2.0 +/- 0.4 micrograms/ml (15 mg/kg), 5.3 +/- 1.0 micrograms/ml (30 mg/kg), 7.4 +/- 1.5 micrograms/ml (60 mg/kg), and 11.1 +/- 2.7 micrograms/ml (120 mg/kg). Mean concentration for all uterine horn fluid samples was 265 +/- 25 ng/ml/horn; range was 79 to 546 ng/ml/horn. The only significant (P = 0.0006) source of variation was the technician performing the flush. Mean concentration for each technician was 184 +/- 24 ng/ml/horn and 345 +/- 35 ng/ml/horn. CLINICAL RELEVANCE: Teratogenic and embryotoxic effects of ABZSO differ for ewes and heifers. Albendazole sulfoxide is detectable in the uterus of heifers; however, ABZSO peaks in heifer plasma earlier and at a lower concentration than that reported for ewes, perhaps contribution to differences in susceptibility at similar dosages.