Pharmacokinetic profile and anthelmintic efficacy of moxidectin administered by different doses and routes to feedlot calves.

We evaluated the comparative plasma disposition kinetics and efficacy of moxidectin (MXD), administered by the intraruminal (IR) or subcutaneous (SC) route at two different dosage levels (0.2 and 1 mg/kg) in feedlot calves. Additionally, the efficacy was compared to an ivermectin (IVM, SC administration) treated group. This study was divided into two separate studies, the "Pharmacokinetic (PK) study" and the "Efficacy study". The "PK study" involved 24 calves free of gastrointestinal nematodes (GIN), which were allocated into 4 groups (n = 6) and treated with MXD by either the SC or the IR route at the therapeutic (MXDSC0.2, MXDIR0.2, respectively) or at fivefold the therapeutic dose (MXDSC1.0, MXDIR1.0, respectively). Blood samples were collected from 3 h up to 14 days post-treatment. MXD concentrations in plasma samples were analyzed by HPLC. The "Efficacy study" included 125 calves naturally infected with GIN, which were allocated into five experimental groups (n = 25 each); the same four MXD-treated groups described for the "PK study", and an additional group treated by the SC route with IVM (IVMSC0.2). The efficacy of IVM given at its therapeutic dose and the different MXD groups at the therapeutic and fivefold the therapeutic dose was calculated by analysis of the individual efficacy using the package eggCounts-2.1-1' on the R software environment, version 3.5.0 (R Core Team, 2018). Daily weight gain (DWG) was also measured over the first 47 days of the fattening cycle. Independently of the administration route, MXD peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) were higher in groups treated with the higher dose (1.0 mg/kg), whereas a longer time to reach Cmax (Tmax) was observed after the IR treatments. The observed MXD efficacies were 85% (MXDSC0.2), 94% (MXDSC1.0), 84% (MXDIR0.2) and 99% (MXDIR1.0), at day +27. At day +27, all MXD-treated groups showed higher efficacies than the group having received IVM (45%). The post-treatment Cooperia spp. L3 counts were particularly low in the groups MXDSC1.0 and MXDIR1.0. All of the groups treated with MXD showed better DWG than the IVMSC0.2 group (P = 0.01). Dose and administration route modifications effectively improved the anthelmintic and productive performance of MXD. A high dose of MXD improved the control of IVM-resistant GIN in feedlot calves. However, this practice must be taken with caution, since MXD resistance could rapidly emerge, especially in grazing cattle.

Impact of ivermectin-resistant gastrointestinal nematodes in feedlot cattle in Argentina / Impacto de nematódeos gastrointestinais ivermectina-resistentes em bovinos em confinamento na Argentina

The aim was to evaluate for 75 days the impact on production of the remaining burden of ivermectin (IVM)-resistant parasites in naturally infected feedlot calves. The herds came from tick-infested areas of cattle breeding where the systematic use of IVM to control tick increases the gastrointestinal parasites resistant to this drug. This investigation was carried out in two commercial feedlots in Buenos Aires province. In feedlot A, two groups of 35 animal each received IVM 1% and the other received ricobendazole (RBZ) 10% respectively. The same was done in feedlot B. On day 0, two groups of 35 animals were made in feedlots A and B. Fecal samples were taken on days 0, 22, 54 and 75 pos-treatment (PT), and body weight was registered, from each animal. Fecal samples were processed for individual count of eggs per gram (EPG) and pooled fecal culture was carried out for identification of the parasite genus in each sampling. Fecal egg count reduction test (FECR) was calculated on day 22 PT. The study design used was a totally randomized block, with commercial feedlot and sex as block variables. For data analysis, a mixed model of the SAS statistical program was used. The FECR average on day 22 was 28.4% in the IVM group, and 94,2 % in the RBZ group . From this date on, significant differences in EPG were kept until day 54. EPG counts were only equal near the end of the trial, on day 75 (p=0.16). In both commercial feedlots, especially in the IVM group, Cooperia spp. was the most prevalent parasite in the fecal cultures. Significant differences in weight (P<0.01) on post-treatment day 75 was found between the average weight in the RBZ and the IVM group (246 vs. 238 kg respectively), what means a difference of 8.3% in gains. The importance for production in the antiparasite failure treatment in commercial feedlots was demonstrated, and the need of pos-treatment controls to evaluate the efficacy of the antiparasitic administered is emphasized.

O objetivo deste trabalho foi avaliar durante 75 dias o impacto sobre a produção da carga de parasita-ivermectina (IVM) resistentes remanescentes em bezerros naturalmente infectados no confinamento. Os rebanhos são provenientes de áreas infestadas por carrapatos, onde o uso sistemático de IVM para o controle do carrapato aumenta a resistência de parasita gastrintestinais a esta droga. Este trabalho foi realizado em dois confinamentos comerciais na província de Buenos Aires. Na fazenda A, dois grupos de 35 animais cada receberam IVM 1% e ricobendazole (RBZ) 10%, respectivamente. O mesmo foi feito no confinamento B. No dia 0, dois grupos de 35 animais foram feitos nas fazendas A e B. As amostras fecais foram tomadas nos dias 0, 22, 54 e 75 pós-tratamento (PT) e o peso corporal foi registrado, de cada animal. Amostras fecais foram processadas para a contagem individual de ovos por grama (EPG). Amostras fecais foram agrupadas para a identificação do gênero parasitária. O teste de redução de ovos fecais (TROF) foi calculado no dia 22 PT. O desenho do estudo utilizado foi aquele dos blocos inteiramente randomizados, sendo confinamento comercial e sexo as variáveis de bloco. Para a análise dos dados, um modelo misto do programa estatístico SAS foi utilizado. A média TROF no dia 22 foi de 28,4% no grupo IVM e 94,2% no grupo RBZ. A partir desta data, diferenças significativas na EPG foram mantidas até o dia 54. Contas de OPG só foram iguais perto do fim do estudo, no dia 75 (p=0,16). Em ambos os confinamentos comerciais, especialmente no grupo IVM, Cooperia spp. foram os parasitos mais prevalentes nas culturas fecais. Diferenças significativas no peso (P<0,01) 75 dias pós-tratamento foram encontradas entre o peso médio nos grupos RBZ e IVM (246 vs 238 kg, respectivamente), o que significa uma diferença de 8,3% nos ganhos. A importância para a produção no tratamento da insuficiência antiparasitários em confinamento comercial foi demonstrada, bem como a necessidade de controles pós-tratamento para avaliar a eficácia dos antiparasitários administrados é enfatizada.