Fernanda Imperiale - Academia.edu (original) (raw)

Papers by Fernanda Imperiale

General pharmacology: avermectins and milbemycinsMechanism of action: ecto-endoparasiticidal acti... more General pharmacology: avermectins and milbemycinsMechanism of action: ecto-endoparasiticidal activity pharmacokinetics - exchange between bloodstream and target tissues - metabolism. Bile and intestinal excretion. Involvement of drug transport systems. Pharmacokinetic-pharmacodynamic relationship. Therapeutic uses: animal species-specific considerations. Resistance available pharmaceutical preparations. Drug and host-related factors affecting pharmacokinetics and efficacy in ruminants.Tissue residues. Withdrawal times. Safety and toxicity. Ecotoxicological impact. Concluding remarks.Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veter...

International Journal for Parasitology: Drugs and Drug Resistance

Se evaluó la estabilidad química de los residuos de ivermectina (IVM, fármaco antiparasitario) en... more Se evaluó la estabilidad química de los residuos de ivermectina (IVM, fármaco antiparasitario) en leches bovina y ovina. La estabilidad del fármaco se midió mediante cromatografía liquida de alta performance analizando muestras de leche con residuos de IVM antes y después del tratamiento térmico. Además se evaluó, mediante la prueba del yogur y estudios microbiológicos de recuento de bacterias lácticas, el efecto de los residuos sobre la viabilidad de las bacterias ácido lácticas. Los residuos de IVM en leche demostraron ser estables a los tratamientos térmicos utilizados en la industria láctea de pasteurización: baja temperatura/largo tiempo (LTLT 65ºC, 30 min) y alta temperatura/corto tiempo (HTST 75ºC, 15 s). Los procesos de industrialización de la leche basados en la actividad de las bacterias lácticas tampoco fueron afectados por la presencia de residuos de IVM. Las concentraciones evaluadas no modificaron el incremento de la acidez en la prueba del yogur y no disminuyeron los recuentos de bacterias lácticas presentes en muestras de yogures elaborados con residuos del antiparasitario. El impacto de los residuos de fármacos antiparasitarios en los procesos tecnológicos de elaboración de alimentos y en la salud del consumidor a largo plazo debe ser cuidadosamente analizado. Palabras clave: leche, residuos de ivermectina, estabilidad térmica, fermentación acido láctica, bacterias ácido lácticas.

Animals, 2021

The prolonged persistence of milk residual concentration of different antiparasitic drugs in lact... more The prolonged persistence of milk residual concentration of different antiparasitic drugs in lactating dairy animals should be considered before recommending their use (label or extra-label) for parasite control in dairy animals. The partition blood-to-milk ratio for different antiparasitic compounds depends on their ability to diffuse across the mammary gland epithelium. The high lipophilicity of some of the most widely used antiparasitic drugs explains their high partition into milk and the extended persistence of high residual concentrations in milk after treatment. Most of the antiparasitic drug compounds studied were shown to be stable in various milk-related industrial processes. Thus, the levels of residues detected in raw milk can be directly applicable to estimating consumer exposure and dietary intake calculations when consuming heat-processed fluid milk. However, after milk is processed to obtain milk products such as cheese, yogurt, ricotta, and butter, the residues of l...

Journal of Veterinary Pharmacology and Therapeutics, 2017

Revista Veterinaria, 2016

Iezzi, S.; Lifschitz, A.; Sallovitz, J.M.; Lanusse, C.; Imperiale, F.: Impacto de los residuos de... more Iezzi, S.; Lifschitz, A.; Sallovitz, J.M.; Lanusse, C.; Imperiale, F.: Impacto de los residuos de ivermectina en los procesos tecnológicos de la leche y sus derivados. Rev. vet. 26: 2, 93-98, 2015

Journal of Food Protection, 2006

Eprinomectin (EPM) is a broad-spectrum endectocide compound approved for use in dairy cattle with... more Eprinomectin (EPM) is a broad-spectrum endectocide compound approved for use in dairy cattle with a zero milk-withdrawal period, but has not been registered for use in lactating dairy sheep. The pattern of EPM excretion in milk was comparatively characterized following its pour-on administration (500 μg/kg) to lactating dairy sheep at two different stages of lactation. The relationship between milk excretion and plasma disposition kinetics of EPM was characterized. Residual EPM concentrations were assessed during cheese making (whey and curd) and ripening (cheese) by high-performance liquid chromatography and fluorescence detection. EPM was poorly distributed from the bloodstream to the mammary gland and low concentrations were excreted in milk. The level of milk production (early-mid and mid-late lactation) did not affect either the plasma-milk distribution or the pattern of residual concentrations in milk. During cheese making, the highest residual concentrations of EPM were measu...

Veterinary Parasitology, 2016

Eprinomectin (EPM) is a macrocyclic lactone used against endo-ectoparasites without withdrawal ti... more 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. This study assessed EPM efficacy against R. (B.) microplus after topical administration at two dose rates and investigated the relationship between EPM systemic exposure in the host and drug concentrations accumulated in ticks recovered from treated animals. A standardized pharmaco-parasitological study was performed in two phases. In phase 1 eighteen Braford cattle naturally infected with R. (B.) microplus were divided into three experimental groups with a similar level of infestation (Kruskal-Wallis test, P>0.05): control group and treated groups with EPM pour-on (1 and 1.5mg/kg). Samples of heparinized blood and ticks at different life stages were taken between 0 and 21 days (d) post-administration to measure EPM concentrations by HPLC. The efficacy trial (phase 2) included eighteen Braford calves naturally infected with R. (B.) microplus divided into control group and 1mg/kg and 1.5mg/kg EPM treated groups. Female ticks (4.5-8mm) on cattle were counted between 1 and 23 days post-treatment to evaluate the efficacy of EPM. The reproductive efficiency index (REI) and the fertility efficiency index (FEI) were evaluated. Plasma concentrations of EPM showed a linear relationship with the level of dose rate administered. Peak plasma concentrations were within a range between 13.8 and 90ng/ml, which guarantee milk drug concentrations below the maximum residues level. High EPM concentrations were detected in ticks. EPM concentrations in R. (B.) microplus were correlated to plasma concentrations between 1.25 days and 21 days post-administration (r 0.84; P<0.05). EPM efficacy calculated using the Henderson-Tilton formula was 98.9% and 99.1% (7 days post-administration) and 100% (23 days post-administration) after EPM treatment at 1 and 1.5mg/kg, respectively. EPM administered at 1.5mg/kg also showed a significantly higher deleterious effect on tick fertility as measured by FEI (P<0.01). Therefore, treatment with EPM may be useful for controlling ticks in cattle, particularly in dairy production systems.

Frontiers in Veterinary Science, 2016

Drug metabolism and disposition: the biological fate of chemicals, 2016

In human and mice ATP-binding cassette efflux transporter ABCG2 represents the main route for act... more 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. Animals received MNP (Zolvix, Novartis Animal Health Inc.) once (2.5 mg/kg per os) and the concentrations of MNP and the active MNP metabolite MNPSO2 were assessed by high-performance liquid chromatography. Compared with the parent drug MNP, we detected higher MNPSO2 plasma concentrations (expressed as area under the concentration-versus-time curve). Moreover, we observed MNPSO2 excretion into milk of dairy cows with a high milk-to-plasma ratio of 6.75. In mechanistic flux ...

Handbook of cheese in health

Triclabendazole (TCBZ) is a flukicidal halogenated benzimidazole compound. It is the drug of choi... more Triclabendazole (TCBZ) is a flukicidal halogenated benzimidazole compound. It is the drug of choice for treating liver fluke infections in livestock. At the present, in endemic areas as Cajamarca (Peru) where fasciolasis is recognized as a major problem in dairy cattle, parasite control strategies are implemented as regular anthelmintic treatments even during the lactating period. The milk obtained from treated dairy cattle does not have an adequate withdrawal time and it is commercialized as fresh milk, processed in dairy industries or consumed as fresh cheese. The current work was carried out to evaluate the disposition kinetics of TCBZ and its-sulpho metabolites, sulphoxide (TCBZSO) and sulphone (TCBZSO2) in plasma and milk, and to assess the presence of residual concentrations of TCBZ metabolites in cheese elaborated with milk obtained from treated dairy cows. Holstein dairy cows (n=7) were treated with TCBZ (Fasinex® 10%, Novartis) by oral route (12 mg/kg). Blood and milk sampl...

Journal of Veterinary Pharmacology and Therapeutics, 2014

Closantel (CLS) is currently used in programs for the strategic control of gastrointestinal nemat... more Closantel (CLS) is currently used in programs for the strategic control of gastrointestinal nematodes. CLS is extralabel used in different dairy goat production systems. From available data in dairy cows, it can be concluded that residues of CLS persist in milk. The current work evaluated the concentration profiles of CLS in plasma and milk from lactating orally treated dairy goats to assess the residues pattern in dairy products such as cheese and ricotta. Six (6) female Saanen dairy goats were treated orally with CLS administered at 10 mg/kg. Blood and milk samples were collected between 0 and 36 days post-treatment. The whole milk production was collected at 1, 4, 7, and 10 days post-treatment to produce soft cheese and ricotta. CLS concentrations in plasma, milk, cheese, whey, and ricotta were determined by HPLC. The concentrations of CLS measured in plasma were higher than those measured in milk at all sampling times. However, the calculated withdrawal time for CLS in milk was between 39 and 43 days postadministration to dairy goats. CLS residual concentrations in cheese (between 0.93 and 1.8 lg/g) were higher than those measured in the milk used for its production. CLS concentrations in ricotta were sixfold higher than those in the milk and 20-fold higher than those in the whey used for its production. The persistent and high residual concentrations of CLS in the milk and in the cheese and ricotta should be seriously considered before issuing any recommendation on the extralabel use of CLS in dairy goat farms.

Veterinary Parasitology, 2007

Ivermectin (IVM) is a broad-spectrum antiparasitic drug extensively used in veterinary medicine. ... more Ivermectin (IVM) is a broad-spectrum antiparasitic drug extensively used in veterinary medicine. The composition of the pharmaceutical preparation affects IVM absorption and its systemic availability. After the introduction of the first approved IVM formulation (propylene glycol/glycerol formal 60:40) used at 200 mg/kg, different pharmaceutical modifications have been assayed to extend IVM persistent endectocide activity. Recently, IVM 3.15% long-acting (IVM-LA) preparations to be administered at 630 mg/kg to cattle were introduced into the veterinary pharmaceutical market. The work reported here was designed to evaluate the comparative IVM absorption pattern and plasma concentration profiles obtained after subcutaneous administration of the classic pioneer IVM formulation (1%) and two different commercially available IVM-LA preparations (3.15%) to cattle. Twenty-eight Holstein heifers were divided in four experimental groups (n = 7) and treated subcutaneously as follows-Group A: IVM 1% given at 200 mg/kg, Group B: IVM 1% administered at 630 mg/kg, Group C: IVM-LA (A) injected at 630 mg/kg and Group D: IVM-LA (B) given at 630 mg/kg. Blood samples were taken between 0.5 and 90 days post-treatment and IVM plasma concentrations were determined by HPLC with fluorescence detection. There were no differences in the persistence of IVM plasma concentrations after the administration of IVM 1% formulation at the two used dose levels (200 and 630 mg/kg). Higher peak plasma concentration (C max) and shorter mean residence time (MRT) were obtained for IVM 1% given at 630 mg/kg (Group B) compared to the treatments with both IVM-LA preparations. The IVM-LA (A) formulation showed a more extended absorption process than IVM-LA (B) preparation, which accounted for a longer persistence of detectable IVM plasma concentrations. The parasitological implications of the observed differences in peak plasma concentrations (C max values) and in the IVM concentration levels measured from day 20, and afterwards until day 90 post-treatment, between the different preparations assayed need to be elucidated. The characterization of the absorption patterns and kinetic behaviour obtained after injection of these novel long-acting formulations used at three times the therapeutic dose recommended for the classic IVM preparation in cattle is a further contribution to the field.

Veterinary Parasitology, 1999

Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activi... more Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activity of endectocide compounds. This work reports on the disposition kinetics and plasma availability of ivermectin (IVM) after subcutaneous (SC) and intramuscular (IM) administration as an oil-based formulation to cattle. Parasite-free Aberdeen Angus calves (n = 24; 240-280 kg) were divided into three groups (n = 8) and treated (200 microg/kg) with either an IVM oil-based pharmaceutical preparation (IVM-TEST formulation) (Bayer Argentina S.A.) given by subcutaneous (Group A) and intramuscular (Group B) injections or the IVM-CONTROL (non-aqueous formulation) (Ivomec, MSD Agvet) subcutaneously administered (Group C). Blood samples were taken over 35 days post-treatment and the recovered plasma was extracted and analyzed by HPLC using fluorescence detection. IVM was detected in plasma between 12 h and 35 days post-administration of IVM-TEST (SC and IM injections) and IVM-CONTROL formulations. Prolonged IVM absorption half-life (p < 0.05) and delayed peak plasma concentration (p < 0.001) were obtained following the SC administration of the IVM-TEST compared to the IVM-CONTROL formulation. No differences in total plasma availability were observed among treatments. However, the plasma residence time and elimination half-life of IVM were significantly longer after injection of the IVM-TEST formulation. IVM plasma concentrations were above 0.5 ng/ml for 20.6 (CONTROL) and 27.5 days (IVM-TEST SC), respectively (p < 0.05). The modified kinetic behaviour of IVM obtained after the administration of the novel oil-based formulation examined in this trial, compared to the standard preparation, may positively impact on its strategic use in cattle.

Veterinary Parasitology, 2004

The plasma concentration profiles of four randomly chosen ivermectin (IVM) generic formulations (... more The plasma concentration profiles of four randomly chosen ivermectin (IVM) generic formulations (IVM G1-G4) were compared after their subcutaneous (SC) administration to healthy calves. The disposition of other avermectin-type endectocide compounds, doramectin (DRM) and abamectin (ABM), was also assessed in the same pharmacokinetic trial. Forty-two parasite-free Aberdeen Angus male calves were randomly allocated into six treatment groups. Animals in each group (n = 7) received SC treatment (200 g/kg

Veterinary Parasitology, 2005

Endectocide compounds are extensively used for broad-spectrum parasite control and their topical ... more Endectocide compounds are extensively used for broad-spectrum parasite control and their topical administration to cattle is widespread in clinical practice. Pour-on formulations of moxidectin, ivermectin, eprinomectin and doramectin (DRM) are marketed internationally for use in cattle. However, variability in antiparasitic efficacy and pharmacokinetic profiles has been observed. Although the tissue distribution pattern for different endectocide molecules given subcutaneously to cattle has been described, only limited information on drug concentration profiles in tissues of parasite location after topical treatment is available. Understanding the plasma and target tissue kinetics for topically-administered endectocide compounds is relevant to optimise their therapeutic potential. The current work was designed to measure the plasma and gastrointestinal (GI) concentration profiles of DRM following its pour-on administration to calves. The influence of natural licking behaviour of cattle on DRM concentration in mucosal tissue and luminal content of different GI sections was evaluated. The trial was conducted in two experimental phases. In Phase I, the DRM plasma kinetics was comparatively characterised in free-licking and in 2-day licking-restricted (non-licking) calves. The pattern of distribution of topical DRM to mucosal and luminal contents from abomasum, duodenum, ileum, caecum and spiral colon was assessed in free-licking and non-licking calves restricted over 10 days post-administration (Phase II). The prevention of licking caused marked changes on the plasma and GI kinetics of DRM administered pour-on. In 2-day licking restricted calves, DRM systemic availability was significantly lower (29%) than in free licking animals during the first 9 days post-treatment. Following a 10day long licking restriction period, DRM concentrations profiles in both mucosal tissue and luminal contents of the GI tract were markedly higher in animals allowed to lick freely. This enhancement in drug concentrations in free-licking compared to non-licking calves, was particularly pronounced in the abomasal (38-fold higher) and duodenal (six-fold higher) luminal content. As shown earlier for ivermectin, licking behaviour may facilitate the oral ingestion of topically-administered DRM in cattle. This would be consistent with the marked lower drug concentration profiles measured in the bloodstream and GI tract of the animals prevented from licking. The work reported here provides relevant information on the pattern of DRM distribution to the GI tract after pour-on treatment, and contributes to understand the variability observed in the antiparasitic persistence of topically-administered endectocides in cattle. The implications of natural licking in topical treatments are

Veterinary Parasitology, 2008

The therapeutic efficacies of ivermectin (subcutaneous injection) and eprinomectin (topical treat... more The therapeutic efficacies of ivermectin (subcutaneous injection) and eprinomectin (topical treatment) given at two different dosage levels to goats naturally infested with Amblyomma parvum were assessed. Treatments included subcutaneous injection of ivermectin at 0.2 and 0.4 mg/kg and extra-label pour-on administration of eprinomectin at 0.5 and 1 mg/kg b.w. Ivermectin and eprinomectin failed to control Amblyomma parvum on goats. Treatment with ivermectin resulted in a low number of engorged female ticks in relation to untreated control goats and, at the highest dose rate (0.4 mg/kg), the female engorgement weights were significantly lower and the pre-oviposition period significantly longer than those observed in ticks recovered from untreated control goats. The tick efficacy assessment was complemented in a separate group of tick-free goats with a pharmacokinetic characterization of eprinomectin (topically administered at 0.5, 1.0 and 1.5 mg/kg) and ivermectin (subcutaneous treatment given at (0.2 and 0.4 mg/kg) in goats. Heparinized blood samples were taken between 0 and 21 days post-treatment. Higher and more persistent drug plasma concentrations were recovered after the subcutaneous treatment with ivermectin compared to those obtained for eprinomectin topically administered. The understanding of the relationship among the pattern of drug absorption, the kinetic disposition and the resultant clinical efficacy is relevant to improve the poor performance observed for ivermectin and eprinomectin against A. parvum on goats.

Research in Veterinary Science, 1998

Journal of Veterinary Pharmacology and Therapeutics, 2002

Moxidectin (MXD) is a milbemycin endectocide compound active at extremely low dosages against a w... more Moxidectin (MXD) is a milbemycin endectocide compound active at extremely low dosages against a wide variety of nematode and arthropod parasites. Different pharmacological approaches are currently being tested to delay the bile-faecal elimination and to obtain increased systemic availability for endectocide molecules in ruminants. Loperamide (LPM) is an opioid derivative, whose main pharmacological action is to abolish intestinal propulsive peristaltic waves. The influence of LPM on the pattern of faecal excretion of MXD and on its plasma disposition following intravenous (i.v.) and subcutaneous (s.c.) administrations to cattle was evaluated in the current work. Parasite-free calves were treated with MXD given either alone at 200 lg/kg by i.v. (Experiment 1) and s.c. (Experiment 2) administrations or coadministered with LPM subcutaneously injected at 0.4 mg/kg. Blood and faecal samples were collected over a period of 20 (Experiment 1) and 40 (Experiment 2) days post-treatment. The recovered plasma and faecal samples were extracted and analysed by high-performance liquid chromatography (HPLC) using fluorescence detection. Significantly higher MXD plasma concentrations were obtained after the coadministration of MXD + LPM compared with treatments with MXD alone by both routes. The higher MXD plasma concentration profiles measured after the coadministration with LPM accounted for the significantly higher AUC values obtained following the i.v. (> 46%) and s.c. (> 38%) treatments. A reduced MXD body clearance was observed in the presence of LPM. The appearance of MXD in faeces was significantly delayed after the i.v. and s.c. coadministrations of MXD with LPM (T 1/2app ¼ 5.87 and 10.6 h, respectively) than that observed after the treatment with MXD alone (T 1/2app ¼ 3.48 and 5.12 h). A delayed MXD peak concentration in faeces collected from MXD + LPM-treated animals compared with those receiving MXD alone, was observed. The delayed intestinal transit time caused by LPM and a potential competition between MXD and LPM for the P-glycoprotein-mediated bile/intestinal secretion processes, may account for the enhanced MXD systemic availability measured in cattle in the current work.