Dexamethasone treatment interferes with the pharmacokinetics of ivermectin in young cattle

Areskog, Marlene; Samson‐Himmelstjerna, Georg von; Alvinerie, M.; Sutra, J.F.; Höglund, Johan

doi:10.1016/j.vetpar.2012.07.011

Cited by 12 publications

(8 citation statements)

References 39 publications

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“…due to inaccurate estimation of BW) and/or altered drug pharmacokinetics and pharmacodynamics in different animals (e.g. due to nutrition-related variations in fat reserves that may affect the persistent efficacy of ML, erratic absorption of drugs from the site of injection and/or interactions with other co-administered drugs) (González Canga et al., 2008, El-Abdellati et al., 2010, Areskog et al., 2012, Areskog et al., 2014, De Graef et al., 2013). These factors can impair the correct estimation of drug efficacy and detection of AR, particularly in the dose-limiting species C. oncophora .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of ivermectin against gastrointestinal nematodes of cattle in Denmark evaluated by different methods for analysis of faecal egg count reduction

Pena-Espinoza

Thamsborg

Denwood

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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The efficacy of ivermectin (IVM) against gastrointestinal nematodes in Danish cattle was assessed by faecal egg count reduction test (FECRT). Six cattle farms with history of clinical parasitism and avermectin use were included. On the day of treatment (Day 0), 20 naturally infected calves per farm (total n = 120) were stratified by initial faecal egg counts (FEC) and randomly allocated to a treatment group dosed with 0.2 mg IVM kg−1 body weight s.c. (IVM; n = 10) or an untreated control group (CTL; n = 10). Individual FEC were obtained at Day 0 and Day 14 post-treatment and pooled faeces by group were cultured to isolate L3 for detection of Ostertagia ostertagi and Cooperia oncophora by qPCR. Treatment efficacies were analysed using the recommended WAAVP method and two open-source statistical procedures based on Bayesian modelling: ‘eggCounts’ and ‘Bayescount’. A simulation study evaluated the performance of the different procedures to correctly identify FEC reduction percentages of simulated bovine FEC data representing the observed real data. In the FECRT, reduced IVM efficacy was detected in three farms by all procedures using data from treated animals only, and in one farm according to the procedures including data from treated and untreated cattle. Post-treatment, O. ostertagi and C. oncophora L3 were detected by qPCR in faeces of treated animals from one and three herds with declared reduced IVM efficacy, respectively. Based on the simulation study, all methods showed a reduced performance when FEC aggregation increased post-treatment and suggested that a treatment group of 10 animals is insufficient for the FECRT in cattle. This is the first report of reduced anthelmintic efficacy in Danish cattle and warrants the implementation of larger surveys. Advantages and caveats regarding the use of Bayesian modelling and the relevance of including untreated cattle in the FECRT are discussed.

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Section: Discussionmentioning

confidence: 99%

Efficacy of ivermectin against gastrointestinal nematodes of cattle in Denmark evaluated by different methods for analysis of faecal egg count reduction

Pena-Espinoza

Thamsborg

Denwood

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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“…The pharmacokinetic properties of avermectins may to some extent explain why C. oncophora has a higher resilience to the drug than does O. ostertagi . Pharmacokinetic causes of reduced anthelmintic efficacy and how they are affected by body condition are, as yet, little explored in this context, but we have recently shown that simultaneous treatment with dexamethasone interferes with the pharmacokinetics of IVM (Areskog et al, 2012). Such causes of lack of efficacy and their potential involvement in the selection for AR need to be further studied.…”

Section: Discussionmentioning

confidence: 99%

Limited efficacy of pour-on anthelmintic treatment of cattle under Swedish field conditions

Areskog

Ljungström²,

Höglund

2013

International Journal for Parasitology: Drugs and Drug Resistan

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“…It has previously also been shown that factors affecting the pharmacokinetics of IVM clearly affect the efficacy of the drug [44], but the theory of altered pharmacokinetics as a cause of reduced anthelmintic efficacy is still speculative and few investigations have been carried out. Accordingly, further trials under field conditions are needed to test whether the physiological changes FSG undergo during turnout alter the pharamacokinetics of the drug, and how this reduces the efficacy of treatment.…”

Section: Discussionmentioning

confidence: 99%

A controlled study on gastrointestinal nematodes from two Swedish cattle farms showing field evidence of ivermectin resistance

et al. 2014

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BackgroundAnthelmintic resistance (AR) is an increasing problem for the ruminant livestock sector worldwide. However, the extent of the problem is still relatively unknown, especially for parasitic nematodes of cattle. The effect of ivermectin (IVM) (Ivomec inj.®, Merial) was investigated in Swedish isolates of gastrointestinal nematode (GIN) populations showing signs of AR in the field to further characterise the AR status by a range of in vivo and in vitro methods.MethodsThree groups, each of 11 calves, were infected with an equal mixture of third stage larvae (L3) of Cooperia oncophora and Ostertagia ostertagi. Group A was inoculated with an IVM-susceptible laboratory isolate and groups B and C with isolates originating from ‘resistant’ cattle farms. Faecal egg counts (FEC) were monitored from 0 to 45 days post infection (d.p.i.), and L3 were harvested continuously for larval migration inhibition testing (LMIT) and species-specific PCR (ITS2). At 31 d.p.i., one calf from each group was necropsied and adult worms were recovered pre-treatment. At 35 d.p.i., calves from all groups were injected with IVM at the recommended dose (0.2 mg/kg bodyweight). At 45 d.p.i., another two animals from each group were sacrificed and established gastrointestinal worms were collected and counted.ResultsA few animals in all three groups were still excreting eggs (50-150 per g faeces) 10 days post IVM injection. However, there was no significant difference in the FEC reductions in groups A (95%; 95% CI 81-99), B (98%; 92-100) and C (99%; 97-100) between 35 and 44 d.p.i. Furthermore, LMIT showed no significant difference between the three groups. Approximately 100 adult O. ostertagi were found in the abomasum of one calf (group B), whereas low to moderate numbers (400-12 200) of C. oncophora remained in the small intestine of the calves in all three groups at 45 d.p.i. PCR on L3 harvested from faecal samples up to 10 days post treatment showed a ratio of 100% C. oncophora in the calves inoculated with isolates A and B, whereas C also had 8% O. ostertagi.ConclusionsOverall, this experiment showed that the animals were successfully treated according to the Faecal egg count reduction test (FECRT) standard (≥ 95% reduction). However, several adult worms of the dose-limiting species C. oncophora demonstrably survived the IVM treatment.

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Dexamethasone treatment interferes with the pharmacokinetics of ivermectin in young cattle

Cited by 12 publications

References 39 publications

Efficacy of ivermectin against gastrointestinal nematodes of cattle in Denmark evaluated by different methods for analysis of faecal egg count reduction

Efficacy of ivermectin against gastrointestinal nematodes of cattle in Denmark evaluated by different methods for analysis of faecal egg count reduction

Limited efficacy of pour-on anthelmintic treatment of cattle under Swedish field conditions

A controlled study on gastrointestinal nematodes from two Swedish cattle farms showing field evidence of ivermectin resistance

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