Background:Pharmacokineticstudiesonampicillininfoalsarelimited,underscoringarelevantgapinknowledge,particularlyregardingthetreatmentofcriticallyillneonatalfoals. Hypothesis/Objectives:Toevaluatetheadequacyoftheampicillindosingregimeninhospitalizedfoalsand,ifnecessary,suggestalternativedosingstrategiestoachieveeffectiveampicillinconcentrations. Animals:Datawerecollectedfrom12hospitalizedfoals. Methods:Foalsweretreatedwith20mg/kgampicillinintravenouslyevery6h.Plasmasampleswereobtainedwithinthefirst48h,andtheminimuminhibitoryconcentration(MIC)wasdeterminedforpathogen-positivepatients.Ampicillincon-centrationswerequantifiedusingliquidchromatography–tandemmassspectrometry.Apopulationpharmacokineticmodelwasdevelopedusinganonlinearmixed-effectsapproach(stochasticapproximationexpectation–maximizationorSAEMalgorithm),andapharmacodynamicevaluationofdifferentdoseregimenswasconductedusingMonteCarlosimulations. Results:A2-compartmentmodelwithfirst-ordereliminationwasselected.Agesignificantlyinfluencedperipheralcompart-mentvolumeandclearance.Themodeldemonstratedexcellentinternalvalidation,with97%ofobservedvalueswithinpre-dictionintervalsandrobuststability,asconfirmedbybootstrapandvisualpredictivechecks.Pharmacodynamicsimulationsindicatedthatadosageregimenof20mg/kgevery6hachievedoptimalPTA(≥90%)forMICsof0.06-0.25mg/Lwitha50%fT>MICtarget.ForhigherMICsora100%fT>MICtarget,morefrequentdosing(q4h)andhigherdoses(30-40mg/kg)werenecessary. Conclusionsandclinicalimportance:TheresultsfromthesimulationshighlighttheclinicalimportanceofadjustingdosingregimensbasedonfoalcharacteristicsandMICtoensureeffectivetreatment,especiallyincriticallyillfoals.
Bardhi, A., Scala-Bertola, J., Gehring, R., Mariella, J., Freccero, F., Scarpellini, R., et al. (2026). A population pharmacokinetic study of ampicillin therapy in hospitalized foals. JOURNAL OF VETERINARY INTERNAL MEDICINE, 40(1), 1-12 [10.1093/jvimsj/aalag021].
A population pharmacokinetic study of ampicillin therapy in hospitalized foals
Bardhi, AnisaPrimo
;Mariella, Jole;Freccero, Francesca;Scarpellini, Raffaele;Castagnetti, Carolina;Barbarossa, Andrea
Ultimo
2026
Abstract
Background:Pharmacokineticstudiesonampicillininfoalsarelimited,underscoringarelevantgapinknowledge,particularlyregardingthetreatmentofcriticallyillneonatalfoals. Hypothesis/Objectives:Toevaluatetheadequacyoftheampicillindosingregimeninhospitalizedfoalsand,ifnecessary,suggestalternativedosingstrategiestoachieveeffectiveampicillinconcentrations. Animals:Datawerecollectedfrom12hospitalizedfoals. Methods:Foalsweretreatedwith20mg/kgampicillinintravenouslyevery6h.Plasmasampleswereobtainedwithinthefirst48h,andtheminimuminhibitoryconcentration(MIC)wasdeterminedforpathogen-positivepatients.Ampicillincon-centrationswerequantifiedusingliquidchromatography–tandemmassspectrometry.Apopulationpharmacokineticmodelwasdevelopedusinganonlinearmixed-effectsapproach(stochasticapproximationexpectation–maximizationorSAEMalgorithm),andapharmacodynamicevaluationofdifferentdoseregimenswasconductedusingMonteCarlosimulations. Results:A2-compartmentmodelwithfirst-ordereliminationwasselected.Agesignificantlyinfluencedperipheralcompart-mentvolumeandclearance.Themodeldemonstratedexcellentinternalvalidation,with97%ofobservedvalueswithinpre-dictionintervalsandrobuststability,asconfirmedbybootstrapandvisualpredictivechecks.Pharmacodynamicsimulationsindicatedthatadosageregimenof20mg/kgevery6hachievedoptimalPTA(≥90%)forMICsof0.06-0.25mg/Lwitha50%fT>MICtarget.ForhigherMICsora100%fT>MICtarget,morefrequentdosing(q4h)andhigherdoses(30-40mg/kg)werenecessary. Conclusionsandclinicalimportance:TheresultsfromthesimulationshighlighttheclinicalimportanceofadjustingdosingregimensbasedonfoalcharacteristicsandMICtoensureeffectivetreatment,especiallyincriticallyillfoals.| File | Dimensione | Formato | |
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