Bovine kidney tissue/biological fluid correlation for penicillin

Abstract

Penicillin is one of the most commonly misused drugs in steers and dairy cows. In the US, at slaughter the tolerance is 50 ng/g in kidney and other edible tissues. If the tolerance is exceeded, the carcass may not be used for human food. A preslaughter test for penicillin in an easily accessible biological fluid is needed to predict if the concentration of penicillin is below tolerance in the kidney before the bovine is slaughtered. In this study, 12 steers were injected three times with the approved dose (7000 IU) of penicillin at 12-h intervals. Blood and urine samples were collected at intervals after the final dose of penicillin. At each sampling point, one kidney biopsy sample was collected by laparoscopic surgery in the live animal. Another kidney sample was collected at slaughter. Correlations between plasma and kidney concentrations and between urine and kidney concentrations were determined. These correlations predict with 95% confidence that 99% of the animals will have kidney tissue below penicillin tolerance when the plasma concentration of penicillin is below 0.4 ng/mL and/or the urine penicillin concentration is below 140 ng/mL.

Interspecies Mixed-Effect Pharmacokinetic Modeling of Penicillin G in Cattle and Swine

“…According to the results, the CLs of liver, kidney, and muscle compartments all were in good agreement with the CL of peripheral compartment 1, which implies the tissue disposition of penicillin is similar to the PK behavior of peripheral compartment 1. The purpose of adding a tissue com- partment is to overcome the model misspecification from the plasma data only, as the elimination phase of penicillin G is always faster in plasma than in tissue (11,40). The limitation for this model is the lack of tissue concentration collected from 0 to 24 h, which results in a blank time frame for plasma only (19).…”

“…Penicillin G concentrations in tissue are also very important, because the meat may not be used for human food if the tolerance is exceeded. So far, studies have shown that the ratio of penicillin G concentration in the tissue to that in the blood was strongly influenced by the formulation of the drug and the time of sampling (11,18). Individual PK studies cannot characterize the inter-and intrasubject variability.…”

“…To avoid tissue residues of penicillin G, the U.S. Food and Drug Administration (FDA) has established 0.05-ppm and zero-tolerance limits for penicillin G residues in edible tissues of cattle and swine, respectively (10). According to the tolerance limits, at least a 14-day withdrawal interval (WDI) is recommended for the labeled use of penicillin G. However, due to the development of microbial resistance since initial approval of these drugs decades ago, to remain effective penicillin is one of the drugs most commonly used at extralabel doses (11). A reason for the occurrence of violative residues may be the extralabel manner in which penicillin G often is administered to animals at a dose which is higher than the approved label dose, which may significantly influence the levels of antibiotic resistance (12,13).…”

Development and validation of an HPLC method for the determination of seven penicillin antibiotics in veterinary drugs and bovine blood plasma

“…They are derived from the Penicillium mold and belong to the b-lactam group of antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive and Gramnegative organisms [5,6].…”

“…In the majority of papers, HPLC methods utilize UV detection at low wavelengths (f 230 nm) [9,10], although fluorimetric [8] and mass spectrometric detection [7] have also been reported. Sample preparation methods involve deproteinization and extraction techniques, such as LLE or for the most part SPE [1,5,6,13].…”