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Research article2020Peer reviewedOpen access

Exposure to benzylpenicillin after different dosage regimens in growing pigs

Sjolund, Marie; Ekstrand, Carl; Wallgren, Per; Bondesson, Ulf; Pringle, Marit; Bengtsson, Bjorn

Abstract

BackgroundPenicillin is important for treatment of pigs, but data on its absorption and disposition in pigs are sparse. This is reflected by the variation in recommended dosages in the literature. Inadequate dosage may lead to treatment failure and selection of resistant bacteria. To optimize treatment regimens, plasma exposure to benzylpenicillin for two sustained release formulations of procaine benzylpenicillin for intramuscular administration was studied in growing pigs by means of tandem mass spectrometry (UPLC-MS/MS). One formulation was an aqueous suspension, Ethacilin (R) vet (ETH), and the other an oily suspension, Ultrapen vet (UPA). Benzylpenicillin exposure after intravenous administration of potassium benzylpenicillin was also explored. Exposure profiles were first studied after single administrations of the approved dosages in healthy pigs and then after repeated administration of different dosages in pigs inoculated intranasally with an Actinobacillus pleuropneumoniae serotype 2 strain.ResultsAfter intravenous administration of benzylpenicillin (n=6), maximum plasma concentration (C-max), 1860-9318 mu g/L, was observed after 15 min. At four h, plasma concentrations decreased to 15-76 mu g/L. After intramuscular administration of ETH (n=6) C-max, 1000-4270 mu g/L, was observed within one h (t(max)) in 5 pigs but at four h in one pig. C-max for UPA (n=6), 910-3220 mu g/L, was observed within one h in three pigs, but at four or 24 h in three pigs. For both ETH and UPA, the terminal phase was characterized by slow decline compared with intravenous administration. Repeated administration of different dosages of ETH and UPA in pigs inoculated with A. pleuropneumoniae (n=54) showed that the approved dose for UPA (30 mg/kg, qd) but not for ETH (20 mg/kg, qd) gave adequate plasma exposure for bacteria with a penicillin MIC of 500 mu g/L. However, more frequent dosing of ETH (bid) or increased dosage gave an adequate exposure.ConclusionsThe approved dosage of ETH provided insufficient plasma exposure for adequate therapy of infections caused by A. pleuropneumoniae or other bacteria with a penicillin MIC of 500 mu g/L. More frequent ETH dosing (bid) or an increased dosage would improve exposure. The approved dosage of UPA however provided adequate exposure.

Keywords

Actinobacillus pleuropneumoniae; Benzylpenicillin; Dosage regimen; Exposure profile; Pig; Plasma concentration

Published in

Acta Veterinaria Scandinavica
2020, Volume: 62, number: 1, article number: 55Publisher: BMC

    UKÄ Subject classification

    Clinical Science

    Publication identifier

    DOI: https://doi.org/10.1186/s13028-020-00552-0

    Permanent link to this page (URI)

    https://res.slu.se/id/publ/108211