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

Abstract

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 μg/ml (15 mg/kg), 5.3 ± 1.0 μg/ml (30 mg/kg), 7.4 ± 1.5 μg/ml (60 mg/kg), and 11.1 ± 2.7 μg/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 contributing to differences in susceptibility at similar dosages.