Basic and clinical pharmacology contribution to extend anthelmintic molecules lifespan

Lanusse, Carlos; Lifschitz, Adrián Luis; Álvarez, Luis Ignacio Ortega

doi:10.1016/j.vetpar.2015.07.015

Cited by 26 publications

(11 citation statements)

References 87 publications

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“…Furthermore, LEV is widely known to be ineffective against inhibited fourth-stage larvae of Ostertagia spp. (Williams, 1991), which is the predominant stage in naturally infected cattle during spring (Fernández, Fiel, & Steffan, 1999 (Geary et al, 2012;Lanusse, Lifschitz, & Alvarez, 2015). In fact, in the current study, the efficacy against Haemonchus spp.…”

Section: Ostertagia 28%mentioning

confidence: 59%

“…Gastrointestinal parasitism in cattle always involves different parasite genera. Treatment with different anthelmintics administered simultaneously could be expected to lead to effective parasite control, because parasites that survive one active compound included in the combination could be killed by the activity of the other active compound (Geary et al., ; Lanusse, Lifschitz, & Alvarez, ). In fact, in the current study, the efficacy against Haemonchus spp.…”

Section: Discussionmentioning

confidence: 99%

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Pharmaco‐parasitological evaluation of the ricobendazole plus levamisole nematodicidal combination in cattle

Cantón

Ceballos

Dominguez

et al. 2017

Vet Pharm & Therapeutics

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The goals of the current study were to evaluate the potential pharmacokinetic (PK) interactions and the clinical efficacy occurring after the subcutaneous (s.c.) administration of ricobendazole (RBZ) and levamisole (LEV) given both separately and coadministered to calves naturally infected with susceptible gastrointestinal nematodes.The clinical efficacy was shown in two seasons, winter and spring, with predominance of different nematode populations. Groups of 15 calves were treated with RBZ alone, LEV alone and RBZ + LEV combination, and an untreated group was kept as a Control.RBZ and LEV plasma concentrations were quantified by HPLC. The clinical efficacy was determined by the faecal egg count reduction test. RBZ and LEV have similar plasma persistence, being detected in plasma over 24 hr post-treatment. No PK interactions were observed after the combined treatment, with similar PK parameters (p > .05) obtained for the single-drug and the combination-based strategy. In winter, the observed clinical efficacies were 96%, 99% and 100% for groups treated with RBZ, LEV and RBZ + LEV, respectively; however, in spring, the efficacies were 95%, 93% and 96% for the same groups. Remarkably, the combination was the only treatment that achieved 100% clinical efficacy against both Haemonchus spp and Ostertagia spp in winter; but the increased presence of Ostertagia spp. in spring (28% in untreated group) determined a tendency to reduced efficacies compared to winter time (only 10% of Ostertagia spp. in untreated group), even for the combined treatment. Overall, in a scenario where the nematode population is susceptible, the RBZ + LEV treatment may be a valid combination in cattle to delay the development of resistance, especially in winter when this combination achieved 100% of efficacy. Thus, selection of anthelmintic resistance will never occur. In fact, this is one of the greatest challenges for the whole cattle production system: to be one step ahead of anthelmintic resistance.

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Section: Ostertagia 28%mentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Pharmaco‐parasitological evaluation of the ricobendazole plus levamisole nematodicidal combination in cattle

Cantón

Ceballos

Dominguez

et al. 2017

Vet Pharm & Therapeutics

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“…However, potential pharmacokinetic and/or pharmacodynamic interactions between drugs may occur. The modified effect may result from a change in the concentration of either one or both drugs in the organism (pharmacokinetic interaction) or from a change in the relation between drug concentration and response of the organism to the drug (pharmacodynamic interaction) (Lanusse, Lifschitz, & Alvarez, 2015). In this context, the efflux activity of ATPbinding cassette (ABC) transporters represents an important molecular mechanism of clinically relevant drug-drug interactions (Marchetti, Mazzanti, Beijnen, & Schellens, 2007).…”

Section: Discussionmentioning

confidence: 99%

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

Ballent

Viviani

Imperiale

et al. 2017

Vet Pharm & Therapeutics

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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. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO into milk was observed. The milk-to-plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO were not modified in the presence of OFZ. The pattern of MNPSO excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO ) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO ) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the in vivo pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO .

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“…While it is unclear why this occurred, it is possible that the administration of other anthelmintics on day 17 may have had an effect. Interactions between anthelmintic classes, resulting in altered pharmacology, have been recorded ( Lanusse et al., 2015 ) and it is possible that such an interaction, resulting from the administration of albendazole and levamisole when the ewes were moved indoors, may have contributed to the lower than expected levels of moxidectin recorded here. However, moxidectin was measured in the plasma of all lambs whose mothers were treated with this active until they were at least 8 weeks old, confirming the transfer of anthelmintic active to suckling offspring in milk demonstrated previously ( Bogan and McKellar, 1988 , Carceles et al., 2001 , Cerkvenik-Flajs et al., 2007 ).…”

Section: Discussionmentioning

confidence: 82%

Selection for anthelmintic resistant Teladorsagia circumcincta in pre-weaned lambs by treating their dams with long-acting moxidectin injection

Leathwick

Miller

Fraser

2015

International Journal for Parasitology: Drugs and Drug Resistan

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Administration of long-acting anthelmintics to pregnant ewes prior to lambing is a common practice in New Zealand. Today, most of these products contain macrocyclic lactone (ML) actives, which because of their lipophilic nature, are detectable in the milk of treated animals and in the plasma of their suckling offspring. This study was conducted to confirm the transfer of ML actives to lambs in the ewe's milk, and to assess whether this could result in selection for ML resistant nematodes in the lamb. Ninety, twin bearing Romney ewes were treated before lambing with a long-acting injectable formulation of moxidectin, a 100-day controlled release capsule (CRC) containing abamectin and albendazole, or remained untreated. After lambing, seven ewes from each treatment group were selected for uniformity of lambing date and, along with their twin lambs, relocated indoors. At intervals, all ewes and lambs were bled, and samples of ewe's milk were collected, for determination of drug concentrations. Commencing 4 weeks after birth all lambs were dosed weekly with 250 infective larvae (L3) of either an ML-susceptible or –resistant isolate of Teladorsagia circumcinta. At 12 weeks of age all lambs were slaughtered and their abomasa recovered for worm counts. Moxidectin was detected in the plasma of moxidectin-treated ewes until about 50 days after treatment and in their lambs until about day 60. Abamectin was detected in the plasma of CRC-treated ewes until the last sample on day 80 and in the plasma of their lambs until about day 60. Both actives were detectable in milk of treated ewes until day 80 after treatment. Establishment of resistant L3 was not different between the treatment groups but treatment of ewes with moxidectin reduced establishment of susceptible L3 by 70%, confirming the potential of drug transfer in milk to screen for ML-resistance in the suckling lamb.

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Basic and clinical pharmacology contribution to extend anthelmintic molecules lifespan

Cited by 26 publications

References 87 publications

Pharmaco‐parasitological evaluation of the ricobendazole plus levamisole nematodicidal combination in cattle

Pharmaco‐parasitological evaluation of the ricobendazole plus levamisole nematodicidal combination in cattle

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

Selection for anthelmintic resistant Teladorsagia circumcincta in pre-weaned lambs by treating their dams with long-acting moxidectin injection

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