Search

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.

Objective: To investigate the influence of two ventilation modes on the performance of an anaesthetic conserving device (AnaConDa) in piglets., Study Design: Prospective randomized experimental trial., Animals: Eight female piglets weighing 24.7 +/- 2.2 kg., Methods: Anaesthesia was maintained with sevoflurane (in 60% oxygen) delivered from the AnaConDa placed between endotracheal tube (ETT) and Y-piece. Anaesthetic depth was guided using standard clinical parameters. Ventilation mode was volume controlled (VC) during the first and pressure support (PS) during the second period of anaesthesia in four piglets (group 1); the order was reversed in group 2. Anaesthetic gases were sampled before (at the proximal end of the ETT) and after the AnaConDa (Y-piece). Data were analysed using a model I anova, with treatment and group as fixed categorical effects. Using a paired t-test, partial pressures of carbon dioxide (Pe'CO(2)) on both sides of the device were compared., Results: Although the mean administration rate of sevoflurane was comparable in both groups (3.8 +/- 1.8 mL hour(-1)), E'Sevo was higher in group 1, more specifically during the first period (p = 0.035). Less sevoflurane escaped during VC (14.0 +/- 3.4%) compared with PS ventilation (17.2 +/- 5.7%) (p = 0.001). Pe'CO(2) was lower at the Y-piece (6.4 +/- 0.8 kPa, 48 +/- 6 mmHg) compared with the ETT (9.3 +/- 1.4 kPa, 70 +/- 11 mmHg) in both groups and ventilation modes. On average, inspiratory CO(2) tension was 2.0 +/-1.0 kPa (15 +/- 8 mmHg). Respiration rate was comparable in all piglets while tidal volume () and peak inspiratory pressure were lower during VC compared with PS (p < 0.001, p = 0.015 respectively)., Conclusions and Clinical Relevance: The observed differences in E'Sevo concentration and sevoflurane breakthrough were probably related to differences in . The observed high FiCO(2) indicated an excessive dead space with the AnaConDa for these piglets.

The reliability of a silicone double-lumen catheter implanted into the external jugular vein and tunnelled towards the neck region was investigated in eight pigs. Surgery was uneventful without interference with the normal homoeostasis during 8 days. After injection of amoxicillin/clavulanic acid through the distal port of the catheter, analysis of drug components in the simultaneous blood samples obtained by the proximal port and a Venoject system were comparable in one pig. Histological control of the catheterized jugular veins pointed to an acceptable tissue reaction while bacteriological examination of the tip of the catheters was negative in only three animals. A moulding of the intestinal veins was made in a pig cadaver to determine the optimal length of insertion of a silicone portal catheter from the splenic vein towards the portal vein. Surgery was straightforward in four pigs whereby the catheter was exteriorized towards the back region. No complications were encountered during and after surgery for 9 days. The technique of a double-lumen catheter placed into the jugular vein and a transsplenic portal catheter is a useful tool for the study of the pharmacokinetics and also the first-pass effect of drugs in experimental pigs.

A residue depletion study of amoxicillin (AMO) and its major metabolites, amoxicilloic acid (AMA) and amoxicillin diketopiperazine-2',5'-dione, was performed after a single oral (p.o.) and intravenous (i.v.) administration of amoxicillin (20 mg kg (-1)) and amoxicillin/clavulanic acid (20 and 5 mg kg (-1)) to pigs. Animals were slaughtered 12, 36, 48, 60, 72, and 84 h after dosing. Tissue samples were analyzed using liquid chromatography-tandem mass spectrometry. Kidney samples contained high concentrations of amoxicilloic acid metabolite, which depleted much slower from tissues than amoxicillin, both after p.o. (t1/2AMO = 4.5 h vs t1/2AMA = 8 h) and i.v. (t1/2AMO = 4 h vs t1/2AMA = 8 h) administration. Moreover, after oral administration, significantly higher amoxicilloic acid concentrations were measured in liver and kidney than after i.v. administration. The coadministration of amoxicillin with clavulanic acid provoked no significant differences in amoxicilloic acid tissue concentrations as compared to an amoxicillin dosing. The prolonged presence of residues of amoxicilloic acid in edible tissues can play an important role in food safety, because the compound could give rise to a possible health risk, although it is not included in the maximum residue limit legislation.

The pharmacokinetic properties of amoxicillin and clavulanic acid were studied in healthy, fasted pigs after single intravenous (i.v.) and oral (p.o.) dosage of 20 mg/kg of amoxicillin and 5 mg/kg of clavulanic acid. The plasma concentrations of the drugs were determined by validated high-performance liquid chromatographic methods and the pharmacokinetic parameters were calculated by compartmental and noncompartmental analyses. After i.v. administration of the two drugs, plasma concentration-time curves were best described by a three-compartmental open model for amoxicillin and a two-compartmental open model for clavulanic acid. Amoxicillin (with a t(1/2 gamma) = 1.03 h and a clearance of 0.58 L/h.kg) and clavulanic acid (with a t(1/2 beta) of 0.74 h and a clearance of 0.41 L/h.kg) were both rapidly eliminated from plasma. Both drugs had apparently the same volume of distribution of 0.34 L/kg. After p.o. administration of the two drugs, a noncompartmental model was used. Elimination half-lives of amoxicillin and clavulanic acid were not significantly different, i.e. 0.73 and 0.67 h respectively. The mean maximal plasma concentrations of amoxicillin and clavulanic acid were 3.14 and 2.42 mg/L, and these were reached after 1.19 and 0.88 h respectively. The mean p.o. bioavailability was found to be 22.8% for amoxicillin and 44.7% for clavulanic acid.