Effects of ivermectin on development of Calliphora vicina, Robineau-Desvoidy 1830 (Diptera, Calliphoridae).

Ivermectin is one of the most widely used drugs for parasite control. Previous studies have shown a reduction in the abundance and diversity of "non-target" coprophilous organisms due to the presence of ivermectin (IVM) in bovine faecal matter (FM). Due to its breadth of behavioural habits, Calliphora vicina is a suitable dipteran species to evaluate the effects of IVM in FM. The aim of this work was to evaluate the effect of five concentrations of IVM in FM (3000, 300, 100, 30, and 3 ng/g) on the development of C. vicina. The following endpoints were evaluated: survival (between the first larval stage and emergence of new adults), larval development times to pupation and pupation times to adult, and adult emergence (% sex) and LC50. Sampling was performed from larval hatching at 60 and 120 min and at 3, 4, 5, and 12 h, and every 24 h specimens were weighed until pupae were observed. Data were analysed by ANOVA using a non-parametric Kruskal-Wallis test and as a function of elapsed development time and accumulated degree hours (ADH). Mortality at 3000 and 300 ng/g was 100% and 97%, respectively. There were statistically significant delays in adult emergence time (p = 0.0216) and in the ADH (p = 0.0431) between the control group (C) and 100 ng/g. The LC50 was determined at 5.6 ng/g. These results demonstrate the lethal and sub-lethal effects of IVM on C. vicina, while highlighting the usefulness of this species as a bioindicator for ecotoxicological studies.

Effects of faecal residues of moxidectin and doramectin on the activity of arthropods in cattle dung.

Dung invertebrate colonization and degradation levels of faeces from cattle treated with endectocides were studied. Faeces of control and doramectin (DRM) (subcutaneous) and moxidectin (MXD) (subcutaneous and topical) treated animals were deposited on the field from 3 to 21 days post-treatment (pt). Pats were recovered after 6 to 42 days post-deposition (pd). Faecal weight, dry matter, arthropods number, and drugs concentrations were determined. Total arthropods number was higher in control (P<0.0001) than in the other groups from days 3 to 21 pt. Total number of insects recovered on days 3, 11, and 21 pt from control pats was significantly (P<0.001) higher than in treated-animal pats during all the trial. At day 21 pt, the insects' number in dung voided by DRM-treated cattle was (P<0.05) lower than in the other groups. Comparisons of dung degradation among treatments were inconclusive. A lower adverse effect was observed for MXD compared with DRM. No significant degradation of MXD or DRM was observed during the present trial.

Loperamide modifies the tissue disposition kinetics of ivermectin in rats.

Ivermectin (IVM) is a broad-spectrum antiparasitic drug extensively used in human and veterinary medicine that is largely excreted in bile and faeces. Loperamide (LPM) is an opioid derivative that reduces gastrointestinal secretions and motility. Both IVM and LPM have been reported to act as P-glycoprotein substrates (P-GP). The goal of the present work was to study the LPM-induced modifications to the pattern of tissue distribution for IVM. Thirty-six Wistar male rats were randomly allocated to two groups (n = 18) and treated subcutaneously with IVM alone or co-administered with LPM. Rats were killed at different times post-treatment and samples (blood and tissues) were collected and analyzed by HPLC. The presence of LPM induced a marked enhancement in the IVM plasma concentrations, resulting in a significantly higher area under concentration time curve (AUC) value (P < 0.01) than that obtained after the administration of IVM alone. Significantly higher IVM availabilities in the liver tissue and small intestine wall (P < 0.05) were obtained in the presence of LPM. There were no statistically significant differences in drug availability in the large intestinal wall after both treatments. However, LPM induced a marked decrease in the amount of IVM recovered in the large intestinal lumen content. The ratio between IVM concentrations in the large intestinal luminal content and plasma at day 1 post-treatment was 4.64-fold higher in the absence of LPM. The delayed intestinal transit time caused by LPM accounting for an extended plasma-intestine recycling time, and a potential competition between IVM and LPM for the P-GP-mediated bile-intestinal secretion processes, may account for the enhanced IVM systemic availability reported in the current study.

Placental and fetal toxicity of albendazole sulphoxide in Wistar rats.

This work characterized the effects of albendazole sulphoxide (ABZSO) on placental and fetal parameters in Wistar rats on day 20 of gestation. ABZSO was fed in laboratory chow at 0, 2.5, 5, 10, 20 or 30 mg/kg/d from day 6 to 15 of gestation to pregnant rats. Data of resorptions, placental and fetal characteristics and fetal skeletal malformations were recorded. Resorption percentages in the 20 and 30 mg/kg/d groups were significantly higher compared to the control group. Placentas of ABZSO-treated rats had lower weight and smaller size than untreated rats. The fetal weight and size were lower in the 5 mg/kg/d dose compared to no treatment. In the 5, 10 and 20 mg/kg/d groups, reductions in ossification process were observed. ABZSO induced malformations and/or fetal death when orally administered to pregnant rats. This data contributes to characterization of the reproductive toxicity of ABZSO, the main active metabolite of albendazole.

Disposition of doramectin milk residues in lactating dairy sheep.

Doramectin (DRM) is a broad spectrum macrocyclic lactone antiparasitic drug not approved for use in dairy animals. However, DRM and other endectocide compounds are widely used extra-label to control endo- and ectoparasites in dairy sheep. The plasma disposition kinetics and the pattern of DRM excretion in milk were characterized following its subcutaneous administration to lactating dairy sheep. DRM concentration profiles were measured in plasma and milk samples after validation of a specific HPLC-based methodology. DRM was detected between 1 h and 30 days post-treatment. DRM concentrations of 0.48 ng.mL(-1) (plasma) and 1.03 ng.mL(-1) (milk) were measured at 30 days post-treatment. DRM was extensively distributed from the bloodstream to the mammary gland, and large concentrations were excreted in milk. The peak concentrations and total amount of DRM recovered in milk (expressed as area under the concentration versus time curve) were 3-fold higher than those measured in plasma; 2.44% of the total DRM dose was excreted in milk. The long persistence of DRM milk residues should be seriously considered before its extra-label use in dairy animals is recommended.