--> Discussion and Conclusions
TISSUE CONCENTRATIONS OF AMOXICILLIN IN SUCKLING PIGLETS AFTER SINGLE INJECTION OF VETRIMOXIN® LA
By Krejci R.1, Guyonnet J.1, Robert N.1, Malasek J.2, Honzlova A.3
1Ceva, Libourne, France; 2Veterinary consultant, Zdar n Sazavou, Czech Rep.; 3State Veterinary Institute, Jihlava, Czech Rep.
Amoxicillin is one of the most frequently used antibiotics in pigs for the treatment and prophylaxis of various pathologies. The long acting injectable forms allow controlled individual treatment of sick animals or animals at the imminent risk of infection.
Suckling piglets in industrial farms are exposed to highly contagious early colonizers such as Streptococcus suis (S. suis) or Haemophilus parasuis (H. parasuis), invasive bacteria able to spread quickly into various tissues of the infected individual. The blood concentrations of amoxicillin, which is the antibiotic of choice in the control of such infections, were well documented after a single injection of the long acting preparations. There is, however very limited knowledge about the concentrations in tissues.
Materials and Methods
Healthy suckling piglets of the weight about 4 kg were injected once with the doses of either 0.1ml per kg lbw or 0.5ml per kg lbw with Vetrimoxin® LA, Ceva (150mg amoxicillin trihydrate in 1 ml). Five piglets were included in each dose group.
Animals were euthanized 2 hours later which corresponds to the Tmax previously assessed by the PK study with Vetrimoxin® LA in 30kg pigs. Blood, synovial fluid and tissues of brain, tonsils and lungs were collected at this time from each of tested piglets. Samples were examined using HLPC/MS/MS method for the quantifiation of amoxicillin.
The results revealed the average concentrations in the brain, lungs, tonsils, blood and synovial flid: 0.08 μg/g, 0.06 μg/g, 0.08 μg/g, 4.12 μg/ml and 0.03 μg/ml respectively after the dose of 0.1ml.kg lbw (Figure 1) and 0.12 μg/g, 0.20 μg/g, 0.22 μg/g, 11.25 μg/g and 0.15 μg/g respectively after the dose of 0.5ml/kg lbw (Figure 2).
Figure 1 Plasma and tissue concentrations determined 2 hours after the i.m. dose of 15mg/kg
The ratio tissue/plasma ranged between 0.0774 and 0.019, with the highest ratios found in the tonsils and the brain.
Figure 2 Plasma and tissue concentrations determined 2 hours after the i.m. dose of 75mg/kg
The highest ratios tissue/plasma were found in the tonsils and lungs, 0.19 and 0.18 respectively. The plasma concentrations were approximately 3 times higher than the ones achieved after the dose of 15mg/kg, which was 5 times higher.
Discussion and Conclusions
Concentrations in lungs, brain, synovial flid and lymphoid tissue observed in this study in suckling piglets were approximately within the same rank of values as reported by Agerso et al. (1998). It means that, for instance the period for which the concentration in the synovial fluid is above the MIC for S. suis (0.03 mg/ml, Ceva internal data) lasts about 48 hours after the dose of 15mg/kg.
After the dose of 75 mg/kg (5 x 15 mg/kg), the concentrations measured 2 hours post injection were three times higher than after the dose of 15 mg/kg and did not reach the 5 times equivalent. This is explained by the delay to achieve the Cmax, which also indicates longer duration of the concentrations above the MIC. Further studies are needed to set the full profie of the concentrations in the tissues.
Agerso H. et al., 1998, Res. Vet. Sci., 64, 251-257
(Source: Axis Issue 02 / Sept 2013 - Ceva Asia Pacific - Proceedings APVS 2013)