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The disposition of fenbendazole was studied in rabbits following either oral or intravenous administration. The major metabolites appearing in plasma were fenbendazole sulphoxide (oxfendazole) and fenbendazole sulphone. Calculation of the total urinary and faecal elimination of the drug and of its known metabolites showed that only 40 per cent of the dose was recovered after oral dosing; 29·7 per cent after an intravenous dose. The sulphoxide and sulphone were minor elimination products. The major excretory metabolite was p-hydroxyfenbendazole.

Tissue and fluid changes occurring within tissue chambers were characterised as a function of time after subcutaneous implantation in cattle. Cytological and chemical investigation revealed that the composition of fluid within chambers approached the theoretical composition of true interstitial fluid as time after implantation progressed. Erythrocyte and leucocyte numbers decreased sharply immediately after implantation and had reached stable numbers by 40 days after implantation. At this stage, chamber fluid samples had lower total protein and albumin concentrations, higher K+and Cl−concentrations and lower pH than corresponding blood samples. Despite an ongoing low-grade chronic inflammatory reaction resulting in fibrous encapsulation of chambers, the vascularity of chamber tissue did not diminish with lime after implantation. By 40 days after implantation, the cellular and chemical constituents had stabilised enough to allow use of the model to study drug distribution.

The fractional binding of 14C-salicylic acid and 14C-pentobarbital was studied as a function of age in plasma of the pig, dog, goat and human. The pig exhibited an unusual degree of hypoalbuminemia and low fractional binding of salicylic acid at birth. Albumin levels and the percent binding of salicylic acid were not significantly lower in newborn plasma than in adult plasma of the other species studied. The pig was also exceptional in that the high fractional binding of pentobarbital observed at low Iigand concentrations in plasma of the newborn was not observed in the other species studied. Depletion of albumin in newborn pig plasma did not appreciably affect the binding of pentobarbital. Thus it is suggested that the plasma of the fetal and newborn pig may contain a nonalbuminoid protein, such as a fetal globulin, which is capable of binding pentobarbital but does not have a high avidity for salicylic acid. It apparently does not exist at birth in the plasmas of the other species studied, as depletion of albumin markedly reduced the fractional binding of pentobarbital.