Depletion of Penicillin G Residues in Heavy Sows after Intramuscular Injection. Part I: Tissue Residue Depletion

Abstract

Heavy sows (n = 126) were treated with penicillin G procaine at a 5× label dose (33 000 IU/kg) for 3 consecutive days by intramuscular (IM) injection using three patterns of drug administration. Treatments differed by injection pattern and injection volume. Sets of sows were slaughtered 5, 10, 15, 20, 25, 32, and 39 days after the last treatment; skeletal muscle, kidney, serum, and urine were collected for penicillin G analysis by LC-MS/MS. Penicillin G at withdrawal day 5 averaged 23.5 ± 10.5 and 3762 ± 1932 ng/g in muscle and kidney, respectively. After 15 days of withdrawal, muscle penicillin G residues were quantifiable in only one treated hog (3.4 ng/g) but averaged 119 ± 199 ng/g in kidneys. Using a hypothetical tolerance of 50 ng/g and a natural log-linear depletion model, the withdrawal period required for penicillin depletion to 50 ng/g was 11 days for skeletal muscle and 47 days for kidney.

An integrated experimental and physiologically based pharmacokinetic modeling study of penicillin G in heavy sows

“…The model slightly over predicted the early phase for plasma, liver, and muscle (within twofold difference in Figure and Supporting information Figure ), and greatly over predicted the concentrations of penicillin G in kidneys for both doses (Figure b,e). The exact reason for this over prediction is unknown, but it may be because the measured concentrations in kidney in the present study were fairly low compared to previous two studies (Apley et al, ; Lupton et al, ). By adjusting the kidney partition coefficient value from 10 to 1, the simulation (blacked dashed lines in Figure b,e) better correlated with the measured data for both doses.…”

“…The predicted WDI with label dose after single IM injection is conservative compared to label withdrawal period of 6 days in swine (all use classes). The predicted WDI after 3 repeated IM injections at 5x label dose is also conservative compared to reported WDI of 28 days in heavy sows from Apley et al (Apley et al, ) and is shorter than 51 days for heavy sows estimated in the study of Lupton et al (Lupton et al, ). Note that if the estimated WDI was a fraction of a day, it was rounded up to the next whole day.…”

“…Comparison of model simulations (solid line) and observed data (red circles) for concentrations of penicillin G in the kidney and muscle of heavy sows exposed to PPG via single IM injection (32.5 mg/kg, a,b), and repeated 3 doses of IM injections (32.5 mg/kg, c,d). Experimental data (individual data points) are from previous studies: panel a and b (Apley et al, ); panel c and d (Lupton et al, ). The data points less than LOQ were marked with the 0.5‐fold and 0.2‐fold LOQ using blue circles for illustration purpose.…”

“…The limit of detection (LOD) is shown in each panel using green dash line. LOD for the kidney is 1.8 ng/g and for the muscle is 0.7 ng/g (Lupton et al, )…”

“…The PBPK model for penicillin G in heavy sows was primarily based on a recently published PBPK model for penicillin G in market‐age swine (Li, Gehring, Riviere, & Lin, ) using available values of physiological parameters for sows, and further calibrated with available pharmacokinetic data in heavy sows (Apley et al, ; Lupton et al, ). The experimental data from the current study were used to evaluate the model.…”