A light and electron microscopic study on the synergistic effect of pyrantel and the febantel metabolite febendazole on adult Toxocara canis in vitro.

In the present study, we investigated the in vitro effects on the motility and morphology of tissues and organs of Toxocara canis of the two drug components of Drontal Plus and Welpan, pyrantel and fenbendazole (the active metabolite of the prodrug febantel), both alone and in combination. Although there was no significant difference observable between the effects of the single drugs and the drug combination on worm motility, the synergistic effect of pyrantel and fenbendazole was manifested by morphological alterations seen by light and electron microscopy. Thus, an earlier onset of damage to worm tissues and organs could be observed compared to the application of the individual drugs. In addition, a higher degree of damage and an increased number of vital organs were involved. There was dramatic, significantly greater and irreversible damage to the hypodermis, longitudinal muscle, intestine, nerve cords and genital organs induced by the pyrantel/fenbendazole combination. We hypothesise that these synergistic effects will also take place when dogs are treated either with Drontal Plus or Welpan in which lower dosages will be sufficient to destroy the worms.

In vitro studies on the effects of flubendazole against Toxocara canis and Ascaris suum.

Adult Toxocara canis and Ascaris suum were incubated in vitro in media containing 0.1, 1, 10 or 100 micro g/ml flubendazole in order to study drug-derived effects. This incubation was done for 8 h and repeated (in some groups) after 24 h for another 8 h. The onset and intensity of flubendazole-derived effects were dosage-dependent and time-dependent, i.e. the same grade of damage was reached when incubating for a longer period at a low dosage or for a shorter period in medium containing a high amount (10 or 100 micro g/ml) of flubendazole. A repeated incubation in drug-containing medium was superior to a single exposure. Flubendazole is apparently able to penetrate into the worm's interior via the cuticle. This became evident in worms with sealed orifices, which showed identical damage to worms which were not sealed. The type of tissue damage due to flubendazole was identical in both worm species when exposed to any of the drug dosages used. The principal mode of action of flubendazole was based on the complete reduction of microtubuli-polymerisation inside the parasite's cells. This apparently led to the complete destruction of the hypodermis, muscle layer and intestine. Flubendazole also stopped the formation of gametes. Summarising, even low concentrations of flubendazole (0.1 micro g/ml) led to significant and irreversible damage in all worms studied.