Monepantel-based anthelmintic combinations to optimize parasite control in cattle.

Improvement in the use of existing anthelmintics is a high priority need for the pharmaco-parasitology research field, considering the magnitude and severity of anthelmintic resistance as an important issue in livestock production. In the work described here, monepantel (MNP) was given alone or co-administered with either macrocyclic lactone (ML) or benzimidazole (BZ) anthelmintics to calves naturally infected with ML- and BZ-resistant gastrointestinal (GI) nematodes on two different commercial cattle farms. Both pharmacokinetic (PK) and efficacy assessments were performed.

Pharmacokinetics and milk excretion pattern of eprinomectin at different dose rates in dairy cattle.

This study aimed at determining the plasma disposition kinetics of eprinomectin (EPM) and EPM excretion pattern through milk after topical administration to dairy cattle at the recommended dose of 0.5 mg/kg and at 1 and 1.5 mg/kg.

Monepantel pharmaco-therapeutic evaluation in cattle: Pattern of efficacy against multidrug resistant nematodes.

The goal of the current work was to perform an integrated evaluation of monepantel (MNP) pharmacokinetics (PK) and pharmacodynamics, measured as anthelmintic efficacy, after its oral administration to calves naturally infected with GI nematodes resistant to ivermectin (IVM) and ricobendazole (RBZ) on three commercial farms. On each farm, forty-five calves were randomly allocated into three groups (n = 15): MNP oral administration (2.5 mg/kg); IVM subcutaneous (SC) administration (0.

Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model.

Recently published data indicates that high ivermectin (IVM) concentrations suppress in vitro SARS-CoV-2 replication. Nasal IVM spray administration may contribute to attaining high drug concentrations in nasopharyngeal tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performances of a novel IVM spray formulation were assessed in a pig model.

Doramectin efficacy against Psoroptes ovis in sheep: Evaluation of pharmacological strategies.

The aims of this study were to evaluate the efficacy of two injectable formulations of doramectin (DRM) against Psoroptes ovis in sheep infested under controlled experimental conditions and to characterize the DRM plasma disposition kinetics in the infested animals. To this end, sheep were experimentally infested with a P. ovis strain from a farm with a history of treatment failure, and then treated either with DRM 1% (traditional preparation) on days 0 and 7 or with DRM 3.

Pharmacokinetic-pharmacodynamic assessment of the ivermectin and abamectin nematodicidal interaction in cattle.

In a context of nematodicidal resistance, anthelmintic combinations have emerged as a reliable pharmacological strategy to control gastrointestinal nematodes in grazing systems of livestock production. The current work evaluated the potential drug-drug interactions following the coadministration of two macrocyclic lactones (ML) ivermectin (IVM) and abamectin (ABM) to parasitized cattle using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The kinetic behavior of both compounds administered either separately or coadministered was assessed and the therapeutic response of the combination was evaluated under different resistance scenarios.

Relationship between pharmacokinetics of ivermectin (3.15%) and its efficacy to control the infestation with the tick Rhipicephalus (Boophilus) microplus in cattle.

This study aimed to determine the relationship between the variation in plasma concentration of ivermectin 3.15% over time and its efficacy against the cattle tick Rhipicephalus (Boophilus) microplus. In addition, a trial was conducted to infer if the application of successive treatments with ivermectin 3.

Effects of fenbendazole and triclabendazole on the expression of cytochrome P450 1A and flavin-monooxygenase isozymes in bovine precision-cut liver slices.

Combinations of the anthelmintics fenbendazole (FBZ) and triclabendazole (TCBZ) have shown enhanced efficacy against the liver fluke Fasciola hepatica. This study aimed to measuring the constitutive expression of CYP1A1, CYP1A2, FMO1 and FMO3, thought to be involved in the metabolism of those compounds, by using an absolute quantitative real time (RT)-PCR approach in bovine precision-cut liver slices (PCLS). It also aimed to characterize the effects of FBZ and TCBZ (alone and in combination) on the expression and activity of the aforementioned isozymes.

Assessment of the long-acting ivermectin formulation in sheep: Further insight into potential pharmacokinetic interactions.

The aim of the current study was to evaluate the in vivo pharmacokinetic of ivermectin (IVM) after the administration of a long-acting (LA) formulation to sheep and its impact on potential drug-drug interactions. The work included the evaluation of the comparative plasma profiles of IVM administered at a single therapeutic dose (200 μg/kg) and as LA formulation at 630 μg/kg. Additionally, IVM was measured in different gastrointestinal tissues at 15 days posttreatment with both IVM formulations.

Assessment of P-glycoprotein gene expression in adult stage of Haemonchus contortus in vivo exposed to ivermectin.

The efflux transporter P-glycoprotein (P-gp) has been implicated in multidrug resistance of different nematode parasites affecting livestock species. Increased expression of P-gp in nematodes after their in vitro as well as in vivo exposure to anthelmintics suggests a role of P-gp in drug resistance. The current study evaluated the P-gp gene expression in a highly-resistant isolate of the sheep nematode Haemonchus contortus, selected after exposure to ivermectin (IVM) treatments at 10-fold the therapeutic dose.

Effects of the Antiparasitic Drug Moxidectin in Cattle Dung on Zooplankton and Benthic Invertebrates and its Accumulation in a Water-Sediment System.

Two anthelmintic macrocyclic lactones-ivermectin and moxidectin-have revolutionized parasite control in cattle. These drugs are only partly metabolized by livestock, and the main route of excretion is via feces. In seasonally inundated floodplains, cattle feces come into direct contact with surface water.

Work disability in Argentinian patients with systemic lupus erythematosus is prevalent and it is due to ethnic, socioeconomic and disease-related factors.

Objective: To study the prevalence and the associated factors of work disability (WD) in systemic lupus erythematosus (SLE) patients.

Methods: A sample of 419 SLE patients from an observational cross-sectional multicenter study was included. Sociodemographic features, disease characteristics, comorbidities, quality of life, unhealthy behaviors, and work-related factors were measured in a standardized interview.

Role of ABC Transporters in Veterinary Medicine: Pharmaco- Toxicological Implications.

Unlike physicians, veterinary practitioners must deal with a number of animal species with crucial differences in anatomy, physiology and metabolism. Accordingly, the pharmacokinetic behaviour, the clinical efficacy and the adverse or toxic effects of drugs may differ across domestic animals. Moreover, the use of drugs in food-producing species may impose a risk for humans due to the generation of chemical residues in edible products, a major concern for public health and consumer's safety.

Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows.

Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO ) into milk. The goal of this study was to evaluate the presence of potential in vivo drug-drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows.

Aquatic toxicity of ivermectin in cattle dung assessed using microcosms.

Ivermectin (IVM) is a parasiticide widely used for livestock. It is a semisynthetic derivative of avermectin, a macrocyclic lactone produced by Streptomyces avermitilis. This drug is only partly metabolized by livestock; considerable amounts of parent drug are excreted mostly via feces.

The ABCG2 Efflux Transporter in the Mammary Gland Mediates Veterinary Drug Secretion across the Blood-Milk Barrier into Milk of Dairy Cows.

In human and mice ATP-binding cassette efflux transporter ABCG2 represents the main route for active drug transport into milk. However, there is no detailed information on the role of ABCG2 in drug secretion and accumulation in milk of dairy animals. We therefore examined ABCG2-mediated drug transport in the bovine mammary gland by parallel pharmacokinetic studies in lactating Jersey cows and in vitro flux studies using the anthelmintic drug monepantel (MNP) as representative bovine ABCG2 (bABCG2) drug substrate.

Hepatic biotransformation pathways and ruminal metabolic stability of the novel anthelmintic monepantel in sheep and cattle.

Monepantel (MNP) is a new amino-acetonitrile derivative anthelmintic drug used for the treatment of gastrointestinal (GI) nematodes in sheep. The present work investigated the main enzymatic pathways involved in the hepatic biotransformation of MNP in sheep and cattle. The metabolic stability in ruminal fluid of both the parent drug and its main metabolite (monepantel sulphone, MNPSO2 ) was characterized as well.

Ivermectin-loaded lipid nanocapsules: toward the development of a new antiparasitic delivery system for veterinary applications.

Ivermectin (IVM) is probably one of the most widely used antiparasitic drugs worldwide, and its efficacy is well established. However, slight differences in formulation may change the plasma kinetics, the biodistribution, and in consequence, the efficacy of this compound. The present study focuses on the development of a novel nanocarrier for the delivery of lipophilic drugs such as IVM and its potential application in antiparasitic control.

Eprinomectin accumulation in Rhipicephalus (Boophilus) microplus: Pharmacokinetic and efficacy assessment.

Eprinomectin (EPM) is a macrocyclic lactone used against endo-ectoparasites without withdrawal time in milk and meat after its pour-on administration at 0.5mg/kg. Previous experiments evaluated the efficacy of EPM against Rhipicephalus (Boophilus) microplus in cattle.

Influence of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D on expression of P-glycoprotein and cytochrome P450 3A in sheep.

In order to improve calcium and phosphorus balance, beef cattle and dairy cows can be supplemented with vitamin D. However, different vitamin D metabolites have been shown to increase expression of P-glycoprotein (P-gp, MDR1, ABCB1) and cytochrome P450 3A (CYP3A) in rodents as well as in cell culture systems. As such interferences might have an impact on pharmacokinetics of some drugs widely-used in veterinary medicine, we investigated the expression of P-gp, CYP3A, vitamin D receptor (VDR), pregnane X receptor (PXR) and retinoid X receptor α (RXRα) in sheep either treated orally with 6μg/kg body weight (BW) 25-hydroxyvitamin D (OHD) for ten days before sacrifice or 12h after intravenous injection of 0.

Integrated assessment of ivermectin pharmacokinetics, efficacy against resistant Haemonchus contortus and P-glycoprotein expression in lambs treated at three different dosage levels.

The main goals of the current work were: (a) to assess the ivermectin (IVM) systemic exposure and plasma disposition kinetics after its administration at the recommended dose, x5 and x10 doses to lambs, (b) to compare the clinical efficacy of the same IVM dosages in lambs infected with an IVM-resistant isolate of Haemonchus contortus, and (c) to assess the expression of the transporter protein P-glycoprotein (P-gp) in H. contortus recovered at 14 days after administration of the IVM dose regimens. There were two separated trials where IVM was administered either subcutaneously (SC, Experiment I) or intraruminally (IR, Experiment II).

Comparative pharmacokinetic and pharmacodynamic response of single and double intraruminal doses of ivermectin and moxidectin in nematode-infected lambs.

Aims: To compare the pharmacokinetics, distribution and efficacy (pharmacodynamic response) of intraruminal ivermectin (IVM) and moxidectin (MXD) administered at 0.2 and 0.4 mg/kg to naturally nematode-infected lambs, and to determine the ex vivo accumulation of these anthelmintics by Haemonchus contortus.

Gene expression and enzyme function of two cytochrome P450 3A isoenzymes in rat and cattle precision cut liver slices.

1. Precision-cut liver slices are one of the in vitro models used in studies concerning xenobiotic metabolism. Sparse information on this field is actually available for cattle and other veterinary species.