The pharmacodynamics of the flukicidal salicylanilides, rafoxanide, closantel and oxyclosanide

Mohammed-Ali, N. A. K.; Bogan, J. A.

doi:10.1111/j.1365-2885.1987.tb00089.x

Cited by 50 publications

(29 citation statements)

References 16 publications

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“…The ability of younger rats to eliminate the drug faster will reduce the fluke's exposure to the drug and so limit the disruption caused, an effect which was seen in the present study. Liver fluke infection is known to reduce the host's ability to metabolise xenobiotics, including anthelmintics such as nitroxynil, oxyclozanide and rafoxanide (Maffei Facino et al 1984Mohammed-Ali and Bogan 1987; see also review by Behm and Sangster, 1999). Age-related changes in the host's drug-metabolising capacity have also been described in sheep following netobimin administration (McKellar et al 1995).…”

Section: Discussionmentioning

confidence: 97%

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Fasciola hepatica : effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes

Meaney¹,

Fairweather²,

Brennan³

et al. 2003

Parasitology Research

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The ultrastructural changes in Fasciola hepatica induced by the fasciolicide clorsulon were assessed using scanning electron microscopy. At 8 and 44 weeks post-infection, male Sprague-Dawley rats infected with F. hepaticawere dosed orally with clorsulon at a concentration of 12.5 mg/kg and mature flukes recovered from the bile duct after 24 h, 48 h, and 72 h in both experiments. An in vitro incubation was also set up using mature fluke (8 weeks old) incubated with clorsulon for 24 h at a concentration of 10 microg/ml. After 24 h in vivo, the young-mature flukes (8 weeks old) showed significant disruption to the tegumental surface, particularly in the anterior mid-body region, where a distinct band of swelling and blebbing was evident. The band began just behind the ventral sucker and ran posteriorly along both margins. The apical cone region of the fluke was characterised by swelling and blebbing of the surface between the spines. Similar changes were evident after 48 h in vivo, but the disruption was more severe and the mid-body band had spread posteriorly. In approximately half of the specimens recovered after 72 h in vivo, widespread disruption had occurred, with sloughing of the apical membrane or the entire syncytium, over almost all of the oral cone and anterior mid-body. For all time periods, the anterior half of the fluke was more severely affected than the posterior half. No differences were seen between the dorsal and ventral surfaces. Old-mature flukes (44 weeks old) showed regionally similar, but more severe and widespread disruption than that seen in the young-mature flukes. The onset of surface changes occurred more quickly in old-mature flukes as well. Eight-week-old flukes which had been incubated for 24 h in vitro showed surprisingly little disruption, but this may be due to the method by which the drug is taken up by the fluke.

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Section: Discussionmentioning

confidence: 97%

“…Inset shows a higher power image of the exposed basal lamina (bl) posterior to the ventral sucker. Bar 5 lm Michiels et al 1987;Mohammed-Ali and Bogan 1987;Hennessy et al 1989;Alvinerie et al 1991). This opens up the possibility of oral ingestion of these compounds as well.…”

Section: Discussionmentioning

confidence: 98%

Fasciola hepatica : effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes

Meaney¹,

Fairweather²,

Brennan³

et al. 2003

Parasitology Research

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“…Because of its haematophagous behaviour as an adult, F. hepatica is particularly susceptible to drugs which bind to plasma proteins. Several fasciolicides bind to such proteins: the salicylanilides, closantel, rafoxanide and oxyclozanide; the halogenated phenol, nitroxynil; and the benzimidazole derivative, triclabendazole (Mohammed Ali et al 1986;Hennessy et al 1987;Michiels et al 1987;Mohammed-Ali and Bogan 1987;Alvinerie et al 1991aAlvinerie et al , 1991b. Consequently, it is probable that they enter the fluke predominantly via the mouth, that is by oral ingestion.…”

Section: Introductionmentioning

confidence: 96%

A scanning electron microscope study on the route of entry of clorsulon into the liver fluke, Fasciola hepatica

Meaney¹,

Haughey²,

Brennan³

et al. 2004

Parasitol Res

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Three experiments were carried out in vitro to determine the roles of the tegument and gut of Fasciola hepatica in the uptake of the flukicidal drug, clorsulon. Changes to the two surfaces were assessed by scanning electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in clorsulon (10 microg/ml). The gastrodermal surface remained normal and few changes to the tegumental surface were observed. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. The gastrodermal surface was severely disrupted and the gut lamellae were disorganised and necrotic. Swelling of the tegument and blebbing on the tegumental surface were evident, but the changes were not severe. More severe swelling of the tegument was observed in the third experiment, in which flukes were incubated for 24 h in clorsulon (10 microg/ml), with both absorptive surfaces being available for drug uptake. The gastrodermal surface was badly disrupted and the gut lamellae were disorganised and necrotic. Taking the results of the three experiments together, the gastrodermal surface was more affected than the tegument and the greatest disruption to the two surfaces was seen when both routes of entry were available to the fluke. The data support a previous study which indicated that entry of clorsulon into the fluke in vivo is principally by the oral ingestion of drug bound to the red blood cells.

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“…Although the drug has been in use over a long period, there have been few reports on its pharmacokinetics or methods of assay. Mohammed-A1 i and Bogan (1) recently reported that rafoxanide had a half life of 17 days in the plasma of sheep and that it was extensively bound to plasma proteins. They determined the half life value from plasma rafoxanide levels following oral administration of the normal therapeutic dose of 7.5 mg kg-I bodyweight.…”

Section: Rafoxanide (35-diiodo-3'-chloro-4'-[p-chlorophenoxy]mentioning

confidence: 98%

Determination of Rafoxanide in Plasma Using High Performance Liquid Chromatography (HPLC) and in Tissue Using HPLC-Thermospray Mass Spectrometry

Blanchflower

Kennedy

Taylor

1990

Journal of Liquid Chromatography

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Methods are described for the determination in plasma and tissue samples, of the drug rafoxanide which is used to control liver fluke in sheep and cattle.HPLC with UV detection i s used to measure levels of the drug in plasma and combined HPLC-thermospray mass spectrometry is used to measure residue levels in tissue. The methods are both sp cific and sensitive with etection limits o f 0.1 ug ml-' for plasma and 0.02 ug g-f for tissue.

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The pharmacodynamics of the flukicidal salicylanilides, rafoxanide, closantel and oxyclosanide

Cited by 50 publications

References 16 publications

Fasciola hepatica : effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes

Fasciola hepatica : effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes

A scanning electron microscope study on the route of entry of clorsulon into the liver fluke, Fasciola hepatica

Determination of Rafoxanide in Plasma Using High Performance Liquid Chromatography (HPLC) and in Tissue Using HPLC-Thermospray Mass Spectrometry

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