Disease relevance of Closantel

• Intra-leukocyte expression of two-component systems in Ehrlichia chaffeensis and Anaplasma phagocytophilum and effects of the histidine kinase inhibitor closantel [1].
• The macrofilaricidal delayed effect of closantel prodrugs was of interest to prevent anaphylactic shock [2].
• In experiment 2, 9 foals and 9 yearlings received a single oral treatment of 8 mg of closantel/kg of body weight; 3 foals and 3 yearlings were kept as nontreated controls [3].
• The therapy included albumin administration to reduce the acute toxicity of closantel [4].
• Optic neuropathy and retinopathy in closantel toxicosis of sheep and goats [5].

High impact information on Closantel

• Closantel treatment induced lysosomal fusion of the E. chaffeensis inclusion in a human monocytic leukemia cell line, THP-1 cells, implying that functional TCSs are essential in preventing lysosomal fusion of the E. chaffeensis inclusion compartment [6].
• Consequently, the plasma kinetics of closantel reliably reflect its depletion from tissues [7].
• The relative bioavailability of 50% of oral closantel can partly be explained by incomplete absorption [7].
• The distribution of closantel to tissues was limited by its high protein binding [7].
• Closantel binds specifically to ovine serum albumin (K(a) of 9. 3x10(6)M(-1)) at site I, the warfarin/phenylbutazone binding site of albumin Closantel also binds to invertebrate haemocyanin and haemolymph [8].

Chemical compound and disease context of Closantel

• Comparative anthelmintic activity of strategic sustained low-level administration of albendazole in feed pellets compared to single doses of closantel and tetramisole against natural ovine parasitic gastroenteritis [9].

Biological context of Closantel

• These results are consistent with the view that closantel acts as an uncoupler of oxidative phosphorylation by increasing mitochondrial permeability [10].
• However, the utility of closantel for parasite control has been threatened by the emergence of resistance [11].
• It is likely that closantel affects membrane associated processes responsible for fluid and ion homeostasis as well as mitochondrial function [12].
• We review the clinical pharmacokinetics of the currently available anthelmintics used in livestock-imidazothiazoles, tetrahydropyrimidines, benzimidazoles/pro-benzimidazoles, salicylanilides (closantel) and avermectin-type compounds [13].
• It is likely that this inhibition of gametogenesis and vitellogenesis was caused by the effects of closantel treatment on intermediary metabolism in the flukes [14].

Anatomical context of Closantel

• Study of the mode of action of the anti-parasitic 'hydrogenophore', closantel, revealed that mitochondria isolated from livers of untreated rats, 13 weeks after infection with Fasciola hepatica metacercariae, were uncoupled [15].
• New closantel and chlorambucil prodrugs expected to accumulate in the lymphatic system were evaluated on the filaria Molinema dessetae [2].
• Comparative in vitro effects of closantel and selected beta-ketoamide anthelmintics on a gastrointestinal nematode and vertebrate liver cells [16].
• PNU-87407, closantel and PNU-88509 uncoupled oxidative phosphorylation in isolated rat liver mitochondria, inhibiting the respiratory control index (with glutamate or succinate as substrate) by 50% at concentrations of 0.14, 0.9 and 7.6 microM, respectively [16].

Associations of Closantel with other chemical compounds

• Autokinase activities of the three recombinant histidine kinases from E. chaffeensis were inhibited by closantel in vitro [1].
• Evidence was collected to show that this may be a selective process since flukes which had survived exposure to rafoxanide and closantel in vivo (in sheep) had lower activity levels of GST than flukes from untreated sheep [17].
• Oral administration of closantel in a dose of 10 mg/kg plus albendazole in a dose of 5 mg/kg liquid suspension was studied in 75 camels naturally infected with various types of gastrointestinal parasites [18].
• The surface areas of the flukes in the triclabendazole-group were comparable with the untreated controls (141 +/- 51.8 mm2), but the flukes in the closantel group were markedly smaller (43.1 +/- 26.9 mm2) [19].
• The anthelmintic activities of nitroxynil, closantel and rafoxanide were tested in cattle against six- and eight-week-old infections of Fasciola hepatica [20].

Gene context of Closantel

• The method was applied to the determination of closantel in plasma and tissue samples, purified by a solid-phase extraction with C18 cartridges [21].

Analytical, diagnostic and therapeutic context of Closantel

• Kinetics of expulsion of Haemonchus contortus from sheep and jirds after treatment with closantel [22].
• Quantitative determination of Closantel residues in milk by high-performance liquid chromatography with fluorescence detection [23].
• A HPLC method with fluorescence detection for quantitative determination of Closantel residues in milk has been developed and validated [23].
• The estimated monitory benefit per animal from the control of gastrointestinal nematodes using moxidectin or closantel in combination with LEV when compared with animals in the control group were US dollars 26 and 25, respectively [24].
• Closantel administered by intramuscular injection at a dose rate of 2.5 mg/kg bodyweight was 60.0 per cent effective against an eight-week-old F hepatica infection [20].

References