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A comparison was made in the plasma concentration of the major metabolites of amoxicillin (AMO), i.e. amoxicilloic acid (AMA) and amoxicillin diketopiperazine-2',5'-dione (DIKETO) in portal and jugular venous plasma after oral (p.o.) and intravenous (i.v.) AMO administration to pigs, in order to study a possible presystemic degradation of AMO in the gastro-intestinal tract and liver. Almost identical plasma concentration-time curves were obtained for AMO and its metabolites in portal and jugular venous plasma, both after p.o. and i.v. AMO administration. Almost immediately after i.v. AMO administration, high AMA and DIKETO concentrations were measured in plasma, while after p.o. dosing, the metabolites appeared in plasma after almost complete absorption of AMO. No significant differences in pharmacokinetic parameters of AMO, AMA and DIKETO, derived from the concentration-time profiles in portal and jugular venous plasma were calculated, both after i.v. and p.o. AMO administration (P > 0.05). After p.o. administration, the half-life of elimination (t(1/2(el))) for AMA is at least two or three times the t(1/2(el)) of AMO (0.75 h for AMO vs. 2.69 h for AMA), indicating the slower clearance of the metabolite. It could be hypothesized that AMA is only eliminated by glomerular filtration, as its open beta-lactam structure might not be recognized by the transport carrier in the proximal tubule of the kidney. The results of the study indicate that AMO is not substantially metabolized presystemically in the gut and liver. Therefore, it may be assumed that the kidney may be the major organ for AMO biotransformation. Future in vivo and in vitro experiments should be performed to state this hypothesis.

The aim of the study was to investigate whether dietary supplementation with yeast-derived glucomannan protects pigs against the deleterious effects that exposure to aflatoxin B1 (AFB1) or T-2 toxin has on the vaccinal immune response and drug-metabolising enzymes. Three doses of pure mycotoxin (AFB1 trial: 482, 968 and 1,912 µg/kg feed; T-2 toxin trial: 593, 1,155 and 2,067 µg/kg feed) with or without dietary glucomannan supplementation (2 g/ kg feed) were tested in weaned pigs for 28 days. At days 4 and 15 pigs were immunised with ovalbumin to study the humoral and cell-mediated antigen-specific immune responses. The effects of AFB1 and T-2 toxin intake alone in pigs have already been published. In all parameters investigated no differences were apparent between animals receiving the unsupplemented control diet or the control diet containing glucomannan. In the AFB1 trial glucomannan decreased the severity of liver lesions in animals exposed to 968 µg/kg feed. Exposure to both AFB1 and T-2 toxin were associated with impaired phase I liver enzyme activities, but glucomannan demonstrated a limited protective effect on these enzymes. With regard to the immune defence system, both toxins modulated the vaccinal immune response; AFB1 impaired specific cellular response and T-2 toxin the specific humoral response. Glucomannan supplementation restored the ovalbumin-specific lymphocyte proliferation that was delayed in pigs exposed to AFB1, regardless of dose. In the T-2 toxin trial glucomannan supplementation restored anti-ovalbumin immunoglobulin G production, which was significantly reduced in pigs exposed to both medium and high doses of the toxin. In conclusion, glucomannan dietary supplementation demonstrated no deleterious effects in control animals and protective effects against AFB1 and T-2 toxin immunotoxicity during a vaccinal protocol.