Measurement of ivermectin concentrations in target worms and host gastrointestinal tissues: Influence of the route of administration on the activity against resistant Haemonchus contortus in lambs

Lloberas, Mercedes; Álvarez, Luis Ignacio Ortega; Entrocasso, C.; Virkel, G.; Lanusse, Carlos; Lifschitz, Adrián Luis

doi:10.1016/j.exppara.2012.04.014

Cited by 56 publications

(49 citation statements)

References 23 publications

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“…A lower IVM plasma drug exposure (expressed as Cmax and AUC) was observed in the current experiment, compared to that previously reported [15]. This may be related to differences in some experiment-related factors (parasitism, breed, body condition, feed, etc.)…”

Section: Discussioncontrasting

confidence: 74%

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Relative bioavailability and comparative clinical efficacy of different ivermectin oral formulations in lambs

Suárez

Álvarez

Castells³

et al. 2013

BMC Vet Res

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BackgroundSeveral oral ivermectin (IVM) formulations for use in sheep are available in the pharmaceutical veterinary market in different countries. All of them are indicated at the same dose rate to treat the gastrointestinal nematodes. However, there is a lack of information on the relative systemic exposure (plasma bioavailability) and clinical efficacy among oral formulations routinely used in sheep. The main goal of the work reported here was to perform a pharmaco-parasitological assessment of three different IVM oral formulations in lambs infected with multiple resistant gastrointestinal nematodes. The comparative drug systemic exposure (IVM plasma concentrations) and nematodicidal efficacies (clinical efficacy) in lambs were determined for a reference (RF) and two different test (T1, T2) IVM oral formulations. One hundred and fifty six (n= 156) healthy Corriedale lambs, naturally infected with multiple resistant gastrointestinal nematodes were allocated into four experimental groups (n=39). Animals in each group received treatment (200 μg/kg) with either the RF, one of the test IVM formulations or were kept as untreated control. Blood samples were collected over 15 days post-treatment (n=8). The IVM plasma concentrations were measured by high performance liquid chromatography with fluorescence detection. The faecal nematode egg count reduction test (FECRT) (n=39) and evaluation of the clinical efficacy were performed at day 14 post-treatment (n=6), where a predominance of IVM highly resistant nematodes was observed.Results and conclusionsNeither the overall kinetic behaviour nor the IVM systemic exposure differed among all the tested oral formulations. Equivalent efficacy results were obtained for the different preparations, with an evident therapeutic failure to control Haemonchus spp. and Teladorsagia circumcincta, which correlates with a high degree of nematode resistance to IVM.

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Section: Discussioncontrasting

confidence: 74%

“…In Uruguay, the development of anthelmintic resistance in sheep nematodes is not an exception. Resistance to IVM in sheep nematodes increased from 1.2% [22] to 65% [15] between 1996 and 2002. The trial described here demonstrated that current IVM resistance situation at the farm in which the study was conducted, is dramatically serious.…”

Section: Discussionmentioning

confidence: 99%

Relative bioavailability and comparative clinical efficacy of different ivermectin oral formulations in lambs

Suárez

Álvarez

Castells³

et al. 2013

BMC Vet Res

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“…The work described here reports for the first time the comparative in vivo ML concentrations measured in adult H. contortus recovered from infected treated lambs . As it was recently described for IVM (Lloberas et al, 2012), the drug concentrations measured in the abomasal content for the three molecules under investigation reflected the amount of drug accumulated within the adult H. contortus . After the administration of IVM by an enteral route (oral, intraruminal), the access of drug to H. contortus was substantially greater than that obtained following the subcutaneous administration (Lloberas et al, 2012).…”

Section: Discussionmentioning

confidence: 54%

“…As it was recently described for IVM (Lloberas et al, 2012), the drug concentrations measured in the abomasal content for the three molecules under investigation reflected the amount of drug accumulated within the adult H. contortus . After the administration of IVM by an enteral route (oral, intraruminal), the access of drug to H. contortus was substantially greater than that obtained following the subcutaneous administration (Lloberas et al, 2012). This finding may confirm that an advantageous transcuticular pattern of drug uptake may occur for GI located nematodes when lipophilic compounds formulated as a drug solution are orally administered, achieving large availability of soluble drug at the GI lumen.…”

Section: Discussionmentioning

confidence: 54%

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

Álvarez

Entrocasso

et al. 2013

International Journal for Parasitology: Drugs and Drug Resistan

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Graphical abstractHighlights► Macrocyclic lactones share some structural and physico-chemical properties. ► The kinetic-dynamic differences of these compounds should be addressed under in vivo standardized conditions. ► Lower concentrations of moxidectin were obtained in resistant Haemonchus contortus. ► Moxidectin showed a higher efficacy against resistant H. contortus. ► The P-glycoprotein expression in H. contortus was increased after ivermectin treatment.

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“…This was for example observed for the standard anthelmintic ivermectin in lambs infected with Haemonchus contortus residing in the abomasum, but feeding on blood. In more detail, lambs treated with ivermectin intraruminally showed higher ivermectin levels in H. contortus than lambs treated subcutaneously that had higher plasma levels (Lloberas et al., 2012). Also fenbendazole enters Trichuris suis in host pigs via the transcuticular pathway.…”

Section: Introductionmentioning

confidence: 99%

Exposure of Heligmosomoides polygyrus and Trichuris muris to albendazole, albendazole sulfoxide, mebendazole and oxantel pamoate in vitro and in vivo to elucidate the pathway of drug entry into these gastrointestinal nematodes

Cowan

Meier

Neodo

et al. 2017

International Journal for Parasitology: Drugs and Drug Resistan

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Millions of people are treated with anthelmintics to control soil-transmitted helminth infections; yet, drug distribution in the plasma and gastrointestinal tract compartments and the pathway of drug uptake into gastrointestinal nematodes responsible for the pharmacological effect are unknown. We assessed the distribution and uptake of albendazole, albendazole sulfoxide, albendazole sulfone in the hookworm Heligmosomoides polygyrus in vitro and in vivo as well as the distribution and uptake of albendazole, mebendazole, and oxantel pamoate in the whipworm Trichuris muris in vitro and in vivo. Oral and intraperitoneal treatments (100 mg/kg) were studied. Drug quantities in helminths and host compartments (stomach, the contents and mucosa of the small and large intestine, and the plasma) were determined using HPLC-UV/vis and anthelmintic activities were recorded using phenotypic readout. The influence of 1-aminobenzotriazole (ABT), an irreversible and unspecific cytochrome P450 inhibitor, on albendazole disposition in mice harboring H. polygyrus was evaluated. In vivo, albendazole was found in quantities up to 10 nmol per ten H. polygyrus and up to 31 nmol per ten T. muris. ABT did not change the levels of albendazole or its metabolites in the plasma of mice harboring H. polygyrus or in H. polygyrus, whereas drug levels in the gastrointestinal tract of host mice doubled. Mebendazole and oxantel pamoate quantities per ten T. muris were as high as 21 nmol and 34 nmol, respectively. Albendazole revealed a very dynamic distribution and high rate of metabolism, hence, H. polygyrus and T. muris are exposed to albendazole and both metabolites via multiple pathways. Diffusion through the cuticle seems to be the crucial pathway of oxantel pamoate uptake into T. muris, and likely also for mebendazole. No relationship between concentrations measured in helminths and concentrations in plasma, intestinal content and mucosa of mice, or drug efficacy was noted for any of the drugs studied.

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Measurement of ivermectin concentrations in target worms and host gastrointestinal tissues: Influence of the route of administration on the activity against resistant Haemonchus contortus in lambs

Cited by 56 publications

References 23 publications

Relative bioavailability and comparative clinical efficacy of different ivermectin oral formulations in lambs

Relative bioavailability and comparative clinical efficacy of different ivermectin oral formulations in lambs

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

Exposure of Heligmosomoides polygyrus and Trichuris muris to albendazole, albendazole sulfoxide, mebendazole and oxantel pamoate in vitro and in vivo to elucidate the pathway of drug entry into these gastrointestinal nematodes

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