Albendazole sulphoxide enantiomers in pregnant rats' embryo concentrations and developmental toxicity

Three single oral doses (8.5, 10, and 14 mg/kg) of a racemic formulation of albendazole sulphoxide (ABZSO) were administered to pregnant rats on day 10 of gestation. Mother plasma and embryo concentrations of ABZSO enantiomers and albendazole sulphone (ABZSO(2)) were determined 9 h after administration. The (-)-ABZSO enantiomer showed higher peak concentrations in both maternal plasma and embryo than the (+) enantiomer. An increase in embryo concentrations of ABZSO enantiomers and ABZSO(2) was only observed when dose rose to 14 mg/kg. There was an increase in resorption when the dose increased, but significant differences were only found in the higher dose group when compared with the other groups. The incidence of external and skeletal malformations (mostly of the tail, vertebrae and ribs) rose significantly in the 10 mg/kg group, producing almost 20% and 90% of malformed fetuses, respectively, and gross external and skeletal abnormalities in the thoracic region and limbs were also found.     

Transplacental transfer of propofol in pregnant ewes

Propofol is an injectable anaesthetic that is currently used both in veterinary and human medicine for the induction and maintenance of anaesthesia. Although little is known about the pharmacokinetics of propofol in fetuses, it is widely used in obstetric procedures, particularly in caesarean section. This study determines the pharmacokinetics of propofol in pregnant ewes in the last third of pregnancy, and placental transfer and pharmacokinetics in fetuses after the administration of a 6 mg/kg intravenous (i.v.) bolus (phase 1) or a 6 mg/kg i.v. bolus followed by continued infusion of 0.4 mg/kg/min. In ewes, the area under the blood concentration-time curve (AUC) and C(max) (8.6 mgh/mL and 9.5mg/mL, respectively) was higher than those of the fetus (1.6 mgh/mL and 1.19 mg/mL, respectively). The mean half-life was 0.5h in the dam and 1.1h in the fetus.     

Pharmacokinetic Behaviour of Albendazole Sulphoxide Enantiomers in Male and Female Sheep

Benzimidazole anthelmintic drugs are widely used in veterinary practice. Albendazole sulphoxide (ABZSO) is a benzimidazole drug with two enantiomers, as a consequence of a chiral centre in the sulphoxide group. The kinetics of these enantiomers were studied in male and female sheep. Plasma samples were obtained from the animals between 0.5 and 72 h after oral administration of 7.5 mg/kg of a racemic formulation of ABZSO (total-ABZSO). After a liquid–liquid extraction, the samples were analysed by HPLC to determine the concentrations of total-ABZSO and of the sulphone metabolite (ABZSO₂). During the chromatographic analysis, the ABZSO peak was collected and reanalysed by an HPLC technique using a Chiral AGP column to quantify the enantiomeric proportion therein. After kinetic analysis, the AUCs obtained for the (+)-ABZSO were 5.8 and 4.0 times higher than those for the (–)-ABZSO in male and female animals, respectively. The mean residence times were 23.4 and 16.1 h for (+)-ABZSO and 22.2 and 17.4 h for (–)-ABZSO for male and female animals, respectively. The only significant difference between the sexes (p<0.05) was in the T _max of the (–)-ABZSO. Comparing both enantiomers within each sex, significant differences were found in all the kinetic parameters. Finally, no kinetic differences were found between sex for total-ABZSO or ABZSO₂.     

Chronic cryptosporidiosis in Australian elapid snakes: control of an outbreak in a captive colony

An outbreak of chronic cryptosporidiosis resulting in hypertrophic gastritis occurred in a captive colony of Australian elapid snakes. Two species of the genus Notechiswere involved: Notechis ***ater(Black Tiger Snake) and Notechis scutatus (Eastern or Mainland Tiger Snake). The infection was eventually fatal in all 9 affected snakes. Typical histopathological findings of the stomach included mucosal thickening with cystic dilatation of gastric glands, moderate oedema and fibrosis of the lamina propria, and a mild to moderate patchy infiltration of inflammatory cells. Procedures implemented to contain the outbreak included the use of a formaldehyde-based disinfectant, prompt removal of faecal matter, uneaten and regurgitated food from enclosures, and examination of faecal specimens for Cryptosporidium oocysts and other pathogens.     

Effect of age and gender in the pharmacokinetics of albendazole and albendazole sulphoxide enantiomers in goats

The kinetics of albendazole metabolites and albendazole sulphoxide enantiomers were studied in 2- and 14-month-old female and male goats, after a single oral dose administration (10 mg/kg) of an albendazole formulation. Blood samples from the jugular vein were collected at 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 and 54 h post-treatment and analyzed using a high performance liquid chromatography method. In all groups the area under the plasma concentration-time curve (AUC) and peak concentration (C_max) values of (+)-ABZSO were significantly higher than those of (−)-ABZSO. The AUC and C_max values obtained for (+)-ABZSO and (−)-ABZSO in adult animals were higher compared to the results in young animals, showing significant differences except for (+)-ABZSO in female animals. In young animals, independently of gender, the C_max appeared earlier compared to adult animals. The mean residence time (MRT) values were shorter in young animals compared to adult animals for all compounds analyzed. No sex-related differences were found for any of the parameters calculated except for the (+)-ABZSO from adult animals.