Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration

Kilp, S.; Ramirez, Diana; Allan, Mark J; Roepke, Rainer K. A.; Nuernberger, Martin C

doi:10.1186/1756-3305-7-85

Cited by 84 publications

(115 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A 2012 compilation considering the chronology and numbers for introduction of the current insecticides gave the GABA-R targeting compounds as only 1.7% of the total with half of them introduced by 1955 [81]. Newly introduced GABAergic insecticides are flu and afoxolaner used for flea and tick control on cats and dogs [58,[62][63][64][65]. There are also important crop pests highly sensitive to NCA-IIs [24,60,82] indicating possible expanded use on optimization.…”

Section: Prospectsmentioning

confidence: 99%

See 1 more Smart Citation

Novel GABA receptor pesticide targets

Casida

Durkin

2015

Pesticide Biochemistry and Physiology

112

View full text Add to dashboard Cite

The γ-aminobutyric acid (GABA) receptor has four distinct but overlapping and coupled targets of pesticide action importantly associated with little or no cross-resistance. The target sites are differentiated by binding assays with specific radioligands, resistant strains, site-directed mutagenesis and molecular modeling. Three of the targets are for non-competitive antagonists (NCAs) or channel blockers of widely varied chemotypes. The target of the first generation (20th century) NCAs differs between the larger or elongated compounds (NCA-IA) including many important insecticides of the past (cyclodienes and polychlorocycloalkanes) or present (fiproles) and the smaller or compact compounds (NCA-IB) highly toxic to mammals and known as cage convulsants, rodenticides or chemical threat agents. The target of greatest current interest is designated NCA-II for the second generation (21st century) of NCAs consisting for now of isoxazolines and meta-diamides. This new and uniquely different NCA-II site apparently differs enough between insects and mammals to confer selective toxicity. The fourth target is the avermectin site (AVE) for allosteric modulators of the chloride channel. NCA pesticides vary in molecular surface area and solvent accessible volume relative to avermectin with NCA-IBs at 20-22%, NCA-IAs at 40-45% and NCA-IIs at 57-60%. The same type of relationship relative to ligand-docked length is 27-43% for NCA-IBs, 63-71% for NCA-IAs and 85-105% for NCA-IIs. The four targets are compared by molecular modeling for the Drosophila melanogaster GABA-R. The principal sites of interaction are proposed to be: pore V1' and A2' for NCA-IB compounds; pore A2', L6' and T9' for NCA-IA compounds; pore T9' to S15' in proximity to M1/M3 subunit interface (or alternatively an interstitial site) for NCA-II compounds; and M1/M3, M2 interfaces for AVE. Understanding the relationships of these four binding sites is important in resistance management and in the discovery and use of safe and effective pest control agents.

show abstract

Section: Prospectsmentioning

confidence: 99%

“…Several types of evidence establish that isoxazolines [57][58][59][60][61][62][63][64][65][66] and meta-diamides (including mDA-7 [24,67] and BPB-1 [68]) are NCAs but at a different high affinity site(s) than those for compounds acting at the NCA-IA, NCA-IB and AVE targets ( …”

Section: Nca Actionmentioning

confidence: 99%

Novel GABA receptor pesticide targets

Casida

Durkin

2015

Pesticide Biochemistry and Physiology

112

View full text Add to dashboard Cite

show abstract

“…Clinical trials have demonstrated the ectoparasitic efficacy of fluralaner as a gamma-aminobutyric acid (GABA) and glutamategated chloride channel inhibitor with potent selectivity for arthropod neuron receptors, resulting in excess neuronal stimulation and rapid insect death after feeding exposure [9,10]. After oral ingestion by the dog, fluralaner is rapidly absorbed and widely distributed, with a long half-life of 12-15 days.…”

Section: Introductionmentioning

confidence: 99%

Results from a U.S. Dog Owner Survey on the Treatment Satisfaction and Preference for Fluralaner against Flea and Tick Infestations

Lavan¹,

Armstrong²,

Normile³

et al. 2017

J Vet Sci Technol

View full text Add to dashboard Cite

Background: Fluralaner is a potent acaricide and insecticide effective against flea and tick (F/T) infestations on dogs and cats. Fluralaner for dogs can be administered orally as a flavored chew with up to a 12-week redosing interval, about three-fold less frequently than monthly F/T medications. This study surveyed dog owners who currently administer fluralaner to their dogs to determine their level of satisfaction with the product and its perceived benefits compared to monthly medications, including the potential for on-time administration compliance.

show abstract

“…Clinical observations were scheduled to cover the period of highest systemic exposure to milbemycin oxime, praziquantel [2,3] and fluralaner [6]. Therefore, clinical signs associated with the concurrent use, e.g.…”

Section: Resultsmentioning

confidence: 99%

Safety of concurrent treatment of dogs with fluralaner (Bravecto¿) and milbemycin oxime - praziquantel

Walther¹,

Fisara²,

Allan³

et al. 2014

Parasites & Vectors

Self Cite

View full text Add to dashboard Cite

Background: Fluralaner (Bravecto™; Merck/MSD Animal Health) is a novel systemic ectoparasiticide for dogs providing long-acting flea and tick control after a single oral dose. Milbemycin oxime and praziquantel are routinely used to control Dirofilaria immitis and intestinal worm infections in dogs. The safety of concurrent use of fluralaner and a commercially available milbemycin oxime plus praziquantel combination tablet, in particular with regard to gastrointestinal symptoms, was investigated using oral doses at or above the maximum recommended rates. Findings: Some minor and transient clinical findings were observed during the study period; however, none of these was considered to be related to concurrent treatment with fluralaner and milbemycin oxime plus praziquantel, or to the use of either product alone. Conclusions: Concurrent treatment with fluralaner, milbemycin oxime and praziquantel is well tolerated in dogs.

show abstract

Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration

Cited by 84 publications

References 8 publications

Novel GABA receptor pesticide targets

Novel GABA receptor pesticide targets

Results from a U.S. Dog Owner Survey on the Treatment Satisfaction and Preference for Fluralaner against Flea and Tick Infestations

Safety of concurrent treatment of dogs with fluralaner (Bravecto¿) and milbemycin oxime - praziquantel

Contact Info

Product

Resources

About