Comparative tissue pharmacokinetics and efficacy of moxidectin, abamectin and ivermectin in lambs infected with resistant nematodes: Impact of drug treatments on parasite P-glycoprotein expression
The high level of resistance to the macrocyclic lactones has encouraged the search for strategies to optimize their potential as antiparasitic agents. There is a need for pharmaco-parasitological studies addressing the kinetic-dynamic differences between various macrocyclic lactones under standardiz...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Artículo |
| Language: | Inglés |
| Published: |
Elsevier
2019
|
| Subjects: | |
| Online Access: | https://www.sciencedirect.com/science/article/pii/S2211320712000334 http://hdl.handle.net/20.500.12123/4775 https://doi.org/10.1016/j.ijpddr.2012.11.001 |
| _version_ | 1855483494631735296 |
|---|---|
| author | Lloberas, María Mercedes Alvarez, Luis Ignacio Entrocasso, Carlos Virkel, Guillermo Leon Ballent, Mariana Maté, María Laura Lanusse, Carlos Edmundo Lifschitz, Adrian Luis |
| author_browse | Alvarez, Luis Ignacio Ballent, Mariana Entrocasso, Carlos Lanusse, Carlos Edmundo Lifschitz, Adrian Luis Lloberas, María Mercedes Maté, María Laura Virkel, Guillermo Leon |
| author_facet | Lloberas, María Mercedes Alvarez, Luis Ignacio Entrocasso, Carlos Virkel, Guillermo Leon Ballent, Mariana Maté, María Laura Lanusse, Carlos Edmundo Lifschitz, Adrian Luis |
| author_sort | Lloberas, María Mercedes |
| collection | INTA Digital |
| description | The high level of resistance to the macrocyclic lactones has encouraged the search for strategies to optimize their potential as antiparasitic agents. There is a need for pharmaco-parasitological studies addressing the kinetic-dynamic differences between various macrocyclic lactones under standardized in vivo conditions. The current work evaluated the relationship among systemic drug exposure, target tissue availabilities and the pattern of drug accumulation within resistant Haemonchus contortus for moxidectin, abamectin and ivermectin. Drug concentrations in plasma, target tissues and parasites were measured by high performance liquid chromatography. Additionally, the efficacy of the three molecules was evaluated in lambs infected with resistant nematodes by classical parasitological methods. Furthermore, the comparative determination of the level of expression of P-glycoprotein (P-gp2) in H. contortus recovered from lambs treated with each drug was performed by real time PCR. A longer persistence of moxidectin (P < 0.05) concentrations in plasma was observed. The concentrations of the three compounds in the mucosal tissue and digestive contents were significant higher than those measured in plasma. Drug concentrations were in a range between 452 ng/g (0.5 day post-treatment) and 32 ng/g (2 days post-treatment) in the gastrointestinal (GI) contents (abomasal and intestinal). Concentrations of the three compounds in H. contortus were in a similar range to those observed in the abomasal contents (positive correlation P = 0.0002). Lower moxidectin concentrations were recovered within adult H. contortus compared to abamectin and ivermectin at day 2 post-treatment. However, the efficacy against H. contortus was 20.1% (ivermectin), 39.7% (abamectin) and 89.6% (moxidectin). Only the ivermectin treatment induced an enhancement on the expression of P-gp2 in the recovered adult H. contortus, reaching higher values at 12 and 24 h post-administration compared to control (untreated) worms. This comparative pharmacological evaluation of three of the most used macrocyclic lactones compounds provides new insights into the action of these drugs. |
| format | Artículo |
| id | INTA4775 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2019 |
| publishDateRange | 2019 |
| publishDateSort | 2019 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | INTA47752019-03-28T16:00:23Z Comparative tissue pharmacokinetics and efficacy of moxidectin, abamectin and ivermectin in lambs infected with resistant nematodes: Impact of drug treatments on parasite P-glycoprotein expression Lloberas, María Mercedes Alvarez, Luis Ignacio Entrocasso, Carlos Virkel, Guillermo Leon Ballent, Mariana Maté, María Laura Lanusse, Carlos Edmundo Lifschitz, Adrian Luis Cordero Abamectina Ivermectina Parásitos Nematoda Plaguicidas Glicoproteínas Lambs Abamectin Ivermectin Parasites Pesticides Glycoproteins Moxidectina The high level of resistance to the macrocyclic lactones has encouraged the search for strategies to optimize their potential as antiparasitic agents. There is a need for pharmaco-parasitological studies addressing the kinetic-dynamic differences between various macrocyclic lactones under standardized in vivo conditions. The current work evaluated the relationship among systemic drug exposure, target tissue availabilities and the pattern of drug accumulation within resistant Haemonchus contortus for moxidectin, abamectin and ivermectin. Drug concentrations in plasma, target tissues and parasites were measured by high performance liquid chromatography. Additionally, the efficacy of the three molecules was evaluated in lambs infected with resistant nematodes by classical parasitological methods. Furthermore, the comparative determination of the level of expression of P-glycoprotein (P-gp2) in H. contortus recovered from lambs treated with each drug was performed by real time PCR. A longer persistence of moxidectin (P < 0.05) concentrations in plasma was observed. The concentrations of the three compounds in the mucosal tissue and digestive contents were significant higher than those measured in plasma. Drug concentrations were in a range between 452 ng/g (0.5 day post-treatment) and 32 ng/g (2 days post-treatment) in the gastrointestinal (GI) contents (abomasal and intestinal). Concentrations of the three compounds in H. contortus were in a similar range to those observed in the abomasal contents (positive correlation P = 0.0002). Lower moxidectin concentrations were recovered within adult H. contortus compared to abamectin and ivermectin at day 2 post-treatment. However, the efficacy against H. contortus was 20.1% (ivermectin), 39.7% (abamectin) and 89.6% (moxidectin). Only the ivermectin treatment induced an enhancement on the expression of P-gp2 in the recovered adult H. contortus, reaching higher values at 12 and 24 h post-administration compared to control (untreated) worms. This comparative pharmacological evaluation of three of the most used macrocyclic lactones compounds provides new insights into the action of these drugs. EEA Balcarce Fil: Lloberas, María Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce. Laboratorio de Parasitología; Argentina Fil: Alvarez, Luis Ignacio. 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 Veterinaria de Tandil; Argentina Fil: Entrocasso, Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce. Laboratorio de Parasitología; Argentina Fil: Virkel, Guillermo Leon. 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 Veterinaria de Tandil; Argentina Fil: Ballent, Mariana. 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 Veterinaria de Tandil; Argentina Fil: Maté, María Laura. 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 Veterinaria de Tandil; Argentina 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 Veterinaria de Tandil; Argentina Fil: Lifschitz, Adrian Luis. 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 Veterinaria de Tandil; Argentina 2019-03-28T15:51:16Z 2019-03-28T15:51:16Z 2013-12 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://www.sciencedirect.com/science/article/pii/S2211320712000334 http://hdl.handle.net/20.500.12123/4775 2211-3207 2211-3207 https://doi.org/10.1016/j.ijpddr.2012.11.001 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Elsevier International Journal of Parasitology: Drugs and Drug Resistance 3 : 20-27 (December 2013) |
| spellingShingle | Cordero Abamectina Ivermectina Parásitos Nematoda Plaguicidas Glicoproteínas Lambs Abamectin Ivermectin Parasites Pesticides Glycoproteins Moxidectina Lloberas, María Mercedes Alvarez, Luis Ignacio Entrocasso, Carlos Virkel, Guillermo Leon Ballent, Mariana Maté, María Laura Lanusse, Carlos Edmundo Lifschitz, Adrian Luis Comparative tissue pharmacokinetics and efficacy of moxidectin, abamectin and ivermectin in lambs infected with resistant nematodes: Impact of drug treatments on parasite P-glycoprotein expression |
| title | Comparative tissue pharmacokinetics and efficacy of moxidectin, abamectin and ivermectin in lambs infected with resistant nematodes: Impact of drug treatments on parasite P-glycoprotein expression |
| title_full | Comparative tissue pharmacokinetics and efficacy of moxidectin, abamectin and ivermectin in lambs infected with resistant nematodes: Impact of drug treatments on parasite P-glycoprotein expression |
| title_fullStr | Comparative tissue pharmacokinetics and efficacy of moxidectin, abamectin and ivermectin in lambs infected with resistant nematodes: Impact of drug treatments on parasite P-glycoprotein expression |
| title_full_unstemmed | Comparative tissue pharmacokinetics and efficacy of moxidectin, abamectin and ivermectin in lambs infected with resistant nematodes: Impact of drug treatments on parasite P-glycoprotein expression |
| title_short | Comparative tissue pharmacokinetics and efficacy of moxidectin, abamectin and ivermectin in lambs infected with resistant nematodes: Impact of drug treatments on parasite P-glycoprotein expression |
| title_sort | comparative tissue pharmacokinetics and efficacy of moxidectin abamectin and ivermectin in lambs infected with resistant nematodes impact of drug treatments on parasite p glycoprotein expression |
| topic | Cordero Abamectina Ivermectina Parásitos Nematoda Plaguicidas Glicoproteínas Lambs Abamectin Ivermectin Parasites Pesticides Glycoproteins Moxidectina |
| url | https://www.sciencedirect.com/science/article/pii/S2211320712000334 http://hdl.handle.net/20.500.12123/4775 https://doi.org/10.1016/j.ijpddr.2012.11.001 |
| work_keys_str_mv | AT lloberasmariamercedes comparativetissuepharmacokineticsandefficacyofmoxidectinabamectinandivermectininlambsinfectedwithresistantnematodesimpactofdrugtreatmentsonparasitepglycoproteinexpression AT alvarezluisignacio comparativetissuepharmacokineticsandefficacyofmoxidectinabamectinandivermectininlambsinfectedwithresistantnematodesimpactofdrugtreatmentsonparasitepglycoproteinexpression AT entrocassocarlos comparativetissuepharmacokineticsandefficacyofmoxidectinabamectinandivermectininlambsinfectedwithresistantnematodesimpactofdrugtreatmentsonparasitepglycoproteinexpression AT virkelguillermoleon comparativetissuepharmacokineticsandefficacyofmoxidectinabamectinandivermectininlambsinfectedwithresistantnematodesimpactofdrugtreatmentsonparasitepglycoproteinexpression AT ballentmariana comparativetissuepharmacokineticsandefficacyofmoxidectinabamectinandivermectininlambsinfectedwithresistantnematodesimpactofdrugtreatmentsonparasitepglycoproteinexpression AT matemarialaura comparativetissuepharmacokineticsandefficacyofmoxidectinabamectinandivermectininlambsinfectedwithresistantnematodesimpactofdrugtreatmentsonparasitepglycoproteinexpression AT lanussecarlosedmundo comparativetissuepharmacokineticsandefficacyofmoxidectinabamectinandivermectininlambsinfectedwithresistantnematodesimpactofdrugtreatmentsonparasitepglycoproteinexpression AT lifschitzadrianluis comparativetissuepharmacokineticsandefficacyofmoxidectinabamectinandivermectininlambsinfectedwithresistantnematodesimpactofdrugtreatmentsonparasitepglycoproteinexpression |