The pharmacokinetic properties of the developmental Amino-Acetonitrile Derivative (AAD), monepantel and its sulfone metabolite, monepantel sulfone were investigated in sheep following intravenous (i.v.) and oral administrations. The sulfone metabolite was rapidly formed and predominated over monepantel 4 h after dosing, irrespective of the route of administration. The steady-state volume of distribution, total body clearance and mean residence time of monepantel were 7.4 L/kg, 1.49 L/(kg x h) and 4.9 h, respectively and 31.2 L/kg, 0.28 L/(kg x h) and 111 h, respectively for monepantel sulfone. The overall bioavailability of monepantel was 31%, but it was demonstrated that approximately the same amount of monepantel sulfone was produced whether monepantel was given intravenously or orally (AUC((0-infinity)) oral/AUC((0-infinity)) i.v. of 94% for monepantel sulfone), making oral administration a very efficient route of administration for monepantel in terms of the amount of sulfone metabolite generated. Because monepantel sulfone is the main chemical entity present in sheep blood after monepantel administration and because it is also an active metabolite, its pharmacokinetic properties are of primary importance for the interpretation of future residue and efficacy studies. Overall, these pharmacokinetic data aid in the evaluation of monepantel as an oral anthelmintic in sheep.

Summary A radioimmunoassay was developed to detect IgE antibodies to the anaesthetic induction agent thiopentone. Significant levels of thiopentone‐reactive IgE antibodies were found in the sera of two patients who had experienced life‐threatening anaphylactoid reactions following administration of the drug. Inhibition experiments revealed that cross‐reactivity occurs between the drug‐reactive IgE antibodies and four barbiturate analogues pentobarbitone, phenobarbitone, barbitone and methohexital. The assay should supplement skin testing for the detection of patients with potentially lethal sensitivity to thiopentone.

An immunoassay was developed to detect IgE antibodies lo the widely used antibacterial drug trimethoprim. Significant levels of trimclhoprim-reactive IgE antibodies were found in the sera of two patients who had experienced life-threatening allergic reactions following administration of a combination of trimethoprim and sulphamethoxazole. No IgE antibodies reactive with sulphamethoxazole were found in the sera of either patient. Inhibition experiments revealed that a high degree of crossreactivity occurs between the drug-reactive IgE antibodies and two structural analogues of trimethoprim. 6-hydroxy-and 6-chloroirimethoprim. These experiments also indicated that the combining sites ofthe trimethoprim-reactivc IgE antibodies in the two sera were probably complementary to different parts o{ the trimethoprim molecule. The assay should supplement skin testing in determining the offending drug in patients with suspected allergie sensitivity to trimethoprim-sulphamethoxazole complex.

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