Influence of administration route on the biotransformation of amoxicillin in the pig

Abstract

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.

Early Changes in Microbial Colonization Selectively Modulate Intestinal Enzymes, but Not Inducible Heat Shock Proteins in Young Adult Swine

“…They were fed the rest of their daily feed allowance without supplemental antibiotic afterwards. The amoxicillin dosage used here was intermediate between values found in the literature for pigs (20 mg/kg BW/day [21]) and rats (100 mg/kg BW/day [22]). Amoxicillin was distributed from 10 days before the estimated farrowing date till 21 days after farrowing.…”

Influence of a pig respiratory disease on the pharmacokinetic behaviour of amoxicillin after oral ad libitum administration in medicated feed

“…For this reason, although the analytical procedure could present some degree of unspecificity, it is not apparently reflected in the pharmacokinetic results. On the other hand, the lack of specificity of analytical method could take more relevance when depletion studies are performed, as the amoxicilloic acid concentrations (t 1/2β = 2.69 h) deplete much slower from tissues than amoxicillin (t 1/2β = 0.75 h), which leads to overestimate the drug levels causing errors in the withdrawal time calculations (Reyns et al. , 2009).…”

High resolution mass spectrometry in the identification of transformation products and metabolites from β-lactam antibiotics in thermally treated milk

“…Consequently, the latter is only observed in samples heated at T120. These three compounds have been previously found in cow milk, chicken and pig tissues, plasma, wastewater and river water by diverse research groups [8,10,14,16,18,[22][23][24].…”