Comparative Pharmacokinetics of Gentamicin C₁, C_1a and C₂ in Healthy and Infected Piglets

Gentamicin, an aminoglycoside antibiotic, is a mixture of therapeutically active C₁, C_1a, C₂ and other minor components. Despite its decades-long use in pigs and other species, its intramuscular (IM) pharmacokinetics/pharmacodynamics (PKs/PDs) are unknown in piglets. Furthermore, the PKs of many drugs differ between healthy and sick animals. Therefore, we investigated the PKs of gentamicin after a single IM dose (10 mg/kg) in healthy piglets and piglets that were intranasally co-infected with Actinobacillus pleuropneumoniae and Pasteurella multocida (PM). The plasma concentrations were measured using validated liquid chromatography/mass spectrometry. The gentamicin exposure was 36% lower based on the area under the plasma concentration-time curve and 16% lower based on the maximum plasma concentration (C_max) in the infected piglets compared to the healthy piglets, while it was eliminated faster (shorter half-life and larger clearance) in the infected piglets compared to the healthy piglets. The clearance and volume of distribution were the highest for the C₁ component. C₁, C_1a and C₂ accounted for 22-25%, 33-37% and 40-42% of the total gentamicin exposure, respectively. The PK/PD target for the efficacy of aminoglycosides (C_max/minimum inhibitory concentration (MIC) > 10) could be exceeded for PM, with a greater magnitude in the healthy piglets. We suggest integrating this PK information with antibiotic susceptibility data for other bacteria to make informed antibiotic and dosage regimen selections against piglet infections.