Pharmacokinetics and relative bioavailability of an oral amoxicillin-apramycin combination in pigs

Abstract

A new compound granular premix of amoxicillin (20% w/w dry mass)/apramycin (5% w/w dry mass) was developed, and its pharmacokinetics and relative bioavailability were determined in pigs following oral administration following a cross-over study design. The pharmacokinetic parameters of amoxicillin (t1/2λ = 6.43 ± 4.85h, Cmax = 3.2 ± 1.35 μg·mL-1, Tmax = 1.92 ± 0.58, AUCINF = 8.98 ± 2.11 h·μg·mL-1) and apramycin (t1/2λ = 8.67±4.4h, Cmax = 0.23 ± 0.12 μg·mL-1, Tmax = 2.25 ± 0.82 h, AUCINF = 12.37 ± 8.64h·μg·mL-1) when administered as the amoxicillin-apramycin granular premix did not significantly differ from those for the single-ingredient powder form of each component. The relative bioavailability of amoxicillin following oral administration of the amoxicillin-apramycin granular premix was 22.62% when compared to the intramuscular administration of commercial amoxicillin sodium-powder. This is the first report of a new amoxicillin-apramycin combination which has a potential veterinary application the for prevention and treatment digestive tract infections in pigs.

Clinical Breakpoint of Apramycin to Swine Salmonella and Its Effect on Ileum Flora

“…PK studies on APR were mainly based on PK data in plasma. Previous result showed that the peak plasma concentration of APR was 0.23 µg/mL and reached at 2.25 h, the AUC INF was 1.59 h•µg/mL in plasma after oral administration of 4 mg/kg [24]. The corresponding PK parameters of the C max and AUC INF were lower observed in plasma of pigs and in broiler chickens [25,26].…”

Qualitative risk assessment of homogeneity, stability, and residual concentrations of antimicrobials in medicated feed and drinking water in pig rearing

“…It was not possible to study the consumption of the medicated feed by the (individual) pigs in the current study. However, other studies [9,10,15] show a large variability in feed consumption between pigs housed in the same pen and stable. Given this large variability, the risk is estimated to be 'moderate to high' based on available literature.…”

“…For antimicrobial treatment to be efficacious, several parameters play a crucial role: the choice of the medicine, the homogeneity and stability of the drug in feed or water [6,7], the dose ingested by the individual animal, and drug factors that affect whether or not the pharmacokinetic/pharmacodynamic (PK/PD) breakpoint is reached [8]. Noticeably, high variability in plasma concentrations is observed in individual pigs after the provision of medicated feed [9,10] and drinking water [11][12][13][14]. Several reasons can account for this variability, namely different intake due to social hierarchy and (sub)clinical illness, homogeneity, stability as well as palatability [2,[15][16][17].…”

“…Several reasons can account for this variability, namely different intake due to social hierarchy and (sub)clinical illness, homogeneity, stability as well as palatability [2,[15][16][17]. This raises questions regarding the optimal efficacy of treatment and prudent use of antimicrobials [9][10][11].…”

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 2: Aminoglycosides/aminocyclitols: apramycin, paromomycin, neomycin and spectinomycin

“…The bioavailability of apramycin is very low; about 4% in pigs (Dai et al., 2017 ) and 2% in broilers (Afifi and Ramadan, 1997 ). Very low serum concentrations were also described after oral administration to calves (Ziv et al., 1985 ).…”