Pharmacokinetics of moxidectin in alpacas following administration of an oral or subcutaneous formulation

Cocquyt, Christine M.; Amstel, Sarel van; Cox, Sherry; Rohrbach, Barton W; Martı́n-Jiménez, Tomás

doi:10.1016/j.rvsc.2015.12.011

Cited by 12 publications

(15 citation statements)

References 16 publications

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“…This compares with C max values of 31.7 – 54.6 ng/ml (±2.45 – 16.9 ng/ml) for cattle (Toutain, Campan, Galtier, & Alvinerie, ; Toutain, Upson, Terhune, & McKenzie, ) and 16.3 – 30.8 ng/ml (±2.15 – 3.4 ng/ml) for sheep (Atta & Abo‐Shihada, ; Mariner, McKinnon, & Bogan, ), which are substantially higher figures. A similar trend was reported for moxidectin where the Cmax following SC injection in alpacas with a mean of 4.40 ± 3.09 ng/ml (Cocquyt, Amstel, Cox, Rohrbach, & Martín‐Jiménez, ) compared to much higher values of 39.4 ± 3.4 ng/ml for cattle (Lanusse et al, ) and 8.29 ± 3.14 ng/ml for sheep (Alvinerie, Escudero, Sutra, Eeckhoutte, & Galtier, ). Interestingly, two studies where moxidectin was given subcutaneously in camels also found lower C max values 8.5 – 8.7 ng/ml ± 0.3–0.35 ng/ml (Oukessou, Berrag, & Alvinerie, ; Oukessou, Badri, Sutra, Galtier, Alvinerie, ) than in cattle, which were about double the value for alpacas indicated by Cocquyt et al, () but similar values to those in sheep 8.29 ± 3.14 ng/ml (Alvinerie et al, ).…”

Section: Discussionsupporting

confidence: 74%

“…In a study with camels, the C max was only 3.24 ng/ml (Alvinerie, Escudero, Sutra, Eeckhoutte, & Galtier, 1998). Interestingly, two studies where moxidectin was given subcutaneously in camels also found lower C max values 8.5 -8.7 ng/ml ± 0.3-0.35 ng/ml (Oukessou, Berrag, & Alvinerie, 1999; than in cattle, which were about double the value for alpacas indicated by Cocquyt et al, (2016) but similar values to those in sheep 8.29 ± 3.14 ng/ml (Alvinerie et al, 1998). Thus, taken together with the results from the present study with DRM these findings would suggest that alpacas demonstrate very low levels of macrocyclic lactone anthelmintics in their blood in general and that would further support a need to critically evaluate the required dosage to achieve acceptable efficacy in that species and that even extrapolating from camels may give misleading efficacy estimates.…”

Section: Discussionmentioning

confidence: 93%

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Pharmacokinetics of subcutaneously administered doramectin in alpacas

Lye¹,

Jacob

Pomroy

et al. 2019

Vet Pharm & Therapeutics

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The objective of this research was to evaluate comparative pharmacokinetics of doramectin in alpacas, after subcutaneous administration of 0.2 mg/kg dose. Six healthy adult alpacas, mean age of 5 years ± 1, (three female and three gelded males) of mean bodyweight of 62 kg ± 16 kg with an average body condition scored 2.8 ± 1 out of five, were used in this study. Serial blood samples were collected from the jugular vein before the administration until day 21 afterwards to establish the pharmacokinetics of doramectin after its subcutaneous administration at 0.2 mg/kg dose. The blood samples were analysed using high‐performance liquid chromatography (HPLC), fluorescence detection method with precolumn derivatisation, validated for alpacas. The pharmacokinetic parameters were calculated using a noncompartmental model, and results showed Cmax (6.05 ± 5.34 ng/ml), Tmax (3.83 ± 2.48 days), AUC (62.12 ± 18.86 ng/ml × d), terminal half‐life (6.2 ± 4.9 days) and MRT (11.56 ± 4.43 days). The results of this study showed that the Cmax and AUC were much lower than in cattle and sheep at the same dosage. Tmax remained similar to cattle and sheep. This study presents valuable information about pharmacokinetics of doramectin in alpacas, which can be utilised in its future efficacy studies.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 93%

Pharmacokinetics of subcutaneously administered doramectin in alpacas

Lye¹,

Jacob

Pomroy

et al. 2019

Vet Pharm & Therapeutics

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“…Regarding the sample preparation, most procedures described for MOX residue quantitation in plasma involve clean up steps using solid phase microextraction cartridges (SPME) 8,[11][12][13] and derivatization step. According to literature, the pharmacokinetic (PK) parameters of a veterinary drug vary according to the applied dose, animal species, type of animal and the application site, among others.…”

Section: Introductionmentioning

confidence: 99%

“…2, 2017 step. [8][9][10][11][12][13] Rarely are described analytical methods by using mass spectrometry as a detector for MOX.14 However, it is important to emphasize that analytical methods based on liquid chromatography coupled to mass spectrometry (HPLC-MS) are sufficiently sensitive and selective to quantify the compounds in very low amounts, not being necessary a derivatization step.Regarding the sample preparation, most procedures described for MOX residue quantitation in plasma involve clean up steps using solid phase microextraction cartridges (SPME) 8,11-13 and derivatization step. According to literature, the pharmacokinetic (PK) parameters of a veterinary drug vary according to the applied dose, animal species, type of animal and the application site, among others.…”

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confidence: 99%

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Determination of Moxidectin in Serum by Liquid Chromatography-Tandem Mass Spectrometry and Its Application in Pharmacokinetic Study in Lambs

Baptista¹,

Fernandes²,

Gilaverte³

et al. 2016

Journal of the Brazilian Chemical Society

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The widespread use of moxidectin (MOX), a parasiticide used in the sheep breeding, has induced the parasite resistance in Brazilian farms. As a consequence, the farmers often increase the dose and frequency of drug utilization, and disregards safety of meat or milk. In order to establish adequate therapeutic treatment it is necessary to know the pharmacokinetics of the drug in the animal's body. Thus, high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for the determination of MOX in serum lamb. Serum samples were treated with acetonitrile to precipitate proteins. A clean up by dispersive extraction in solid phase (SPE-d), using primary/secondary amine (PSA) and C18 sorbents, followed by freezing was performed. Method validation presented precision (coefficient of variation) and accuracy (recovery%) between 1.7-6.7 and 80.0-107.3%, respectively. The limit of quantification (LOQ) of the method was 2.0 ng mL -1 and a linear response was obtained over a range of 2.0 to 100 ng mL -1 . This method was successfully applied to the determination of MOX in serum from suffolk lamb to evaluate the pharmacokinetic profile. Keywords: serum lamb, moxidectin, veterinary drug, pharmacokinetic, LC-MS/MS IntroductionThe infections with gastrointestinal nematodes have constituted major obstacle to the expansion of the sheep industry in Brazil. The gastrointestinal parasitism is associated with physiological changes in animals, such as bowel dysfunction and nutritional stress that result in decreased body condition, lower weight gain and death of animals. Among the most important parasites that affect sheep flocks we can highlight the Haemonchus contortus. The parasiticide agents allowed for controlling endo and ecto-parasites in sheep, the macrocyclic lactones, have been widely employed over the world because of its high efficiency and broad-spectrum activity.2 The moxidectin (MOX) (Figure 1), semisynthetic derivative of nemadectin, is a macrocyclic lactone obtained by the fermentation of Streptomyces cyanogriseus. 3 In the last decade MOX has emerged in sheep flocks in Brazil due to its efficacy against a wide variety of nematodes and arthropod parasites, even at extremely low doses. 4 However, similarly as occurred with other drugs, indiscriminate use of MOX could induce parasite resistance, affecting the efficiency of the drug.5 Actually, similarly to ivermectin and the benzimidazole, parasite resistance against MOX has been reported in Brazil. 6 As an action of parasite resistance control, alternatives have been studied in order to minimize the spread of animal diseases and the damage to the breeding and may be referred: correct management and grazing, proper sheep nutrition, selection of resistant animals, biological control, use of vaccines, herbal medicine and/or the use of techniques for assessing the degree of infection. 7Chromatographic methods for the determination of MOX in plasma from different species (alpacas, cattle, horses, pig, rabbit and s...

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