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Selected Publication:

Publication type: Doctoral Thesis

Year: 2003

Author(s): Hierweck, B

Title: Pharmakokinetik und antibakterielle Wirkung von Natrium-Ampicillin in Plasma und Gewebekammerflüssigkeit nach intramuskulärer Injektion beim Pferd.

Source: Dissertation, Vet. Med. Univ. Wien, pp. 77.

Advisor(s):

Van Den Hoven Rene


Project(s): Pharmacocinetics and bactericidal action of penicillin in equine plasma and tissue fluid after intramusculary injection of commercial preparations


Abstract:
In this study the pharmacokinetics of sodium ampicillin and its antimicrobial in vitro activity, in plasma and tissue chamber fluid (TCF) of horses, before and after induction of soft tissue-inflammation, were compared. 6 horses were implanted 1 tissue chamber on either side of the neck subcutaneously in. Each horse received 15 mg/kg sodium ampicillin intramuscularly in trial 1. After about 17 days, 0.5 ml of a 2% carrageenan solution was injected into each tissue chamber about 11.8 h prior to administration of 15 mg/kg sodium ampicillin (trial 2). Ampicillinconcentrations in plasma and TCF were determined by HPLC/MS/MS. The differences of the pharmacokinetic parameters (C_max, t_max, #lambda#Z, t_1/2,VZ/F, Cl/F, AUC, MRT, Ratio_TCF)in plasma of trial 1 and 2 were statistically not significant. The t_1/2 was significantly shorter in trial 2 (5.07#±#1.29 h) than in trial 1 (6.51#±#1.22). Moreover, in both trials the AUC_TCF was smaller than the AUC_Plasma, the C_max in TCF was much lower too than in Plasma. Furthermore, drugconcentrations increased more slowly in TCF than in plasma, but also, after reaching C_max the decrease was more slowly, resulting in a prolonged t_1/2 and MRT. Minimal inhibitory concentrations (MIC´s) for sodium ampicillin were #£#2 µg/ml for all tested microorganisms (St. aureus, St. intermedius, Sc. dysgalactiae sp. equisimilis, Sc. equi sp. equi, Sc. equi sp. zooepidemicus, R. equi). However, in plasma five out of the six bacterial strains had markedly lower MIC´s (#;#0.016 - 0.51 µg/ml). In TCF of trial 1, five bacterial isolates had MIC´s between 1.81 and 3.27 µg/ml, R. equi could not be inhibited. None of the microorganisms, except Sc. dysgalactiae sp. equisimilis (inhibition at a concentration of 4.42 µg/ml), could be inhibited by TCF out of trial 2. Ignoring possible host defence mechanisms, a maximum dose interval of 6 h for sodium ampicillin, at a dose rate of 15 mg/kg IM, should be considered in the horse.

Keywords:
sodium ampicillin, horse, pharmacokinetics, antimicrobial activity, plasma, tissue chamber fluid


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