Pharmacokinetics, tissue residue depletion, and withdrawal interval estimations of florfenicol in goats following repeated subcutaneous administrations.

Florfenicol is a broad-spectrum antibiotic commonly used in the U.S. to treat respiratory and enteric infections in goats in an extra-label manner, which requires scientifically based withdrawal intervals (WDIs) for edible tissues. This study aimed to determine the depletion profiles for florfenicol and florfenicol amine in plasma and tissues samples and to estimate WDIs for goats following subcutaneous injection of 40 mg/kg florfenicol, twice, 96 h apart. The samples were collected up to 50 days after the second dose. Pharmacokinetic parameters were calculated using non-compartmental analysis. Three different pharmacostatistical methods with different operational tolerances were used to calculate WDIs. The plasma half-life was 101.80 h for florfenicol and 207.69 h for florfenicol amine after the second dose. Using the FDA tolerance limit method, WDIs were 202 and 101 days, while the EMA maximum residue limit method estimated 179 and 96 days for the respective tissue concentrations to fall below limits of detection (0.12 µg/g for liver and 0.05 µg/g for kidney). This study characterizes plasma pharmacokinetics and tissue depletion profiles of florfenicol and florfenicol amine in goats following subcutaneous injections and reports estimated WDIs for food safety assessment of florfenicol in goats.

Antibacterial Drug Residues in Small Ruminant Edible Tissues and Milk: A Literature Review of Commonly Used Medications in Small Ruminants.

This review provides a summary of extracted data from the published literature that contains drug residue depletion data for edible tissues and milk following treatment of sheep and goats. Out of 20,234 records obtained during the initial search, data from 177 records were included in this review. The data is separated by antibiotic class for ease of comparison between studies. Extracted data includes the active ingredient, dosing information, animal health status, analytical method and limits of detection, tolerance and maximum residue limit information, and time frames relative to residue absence or detection. This information is useful for understanding drug residue depletion profiles following extra-label use and for estimating withdrawal intervals, in order to protect the human food chain.

Comparison of florfenicol depletion in dairy goat milk using ultra-performance liquid chromatography with tandem mass spectrometry and a commercial on-farm test.

Florfenicol is a broad-spectrum antibiotic commonly prescribed in an extra-label manner for treating meat and dairy goats. Scientific data in support of a milk withdrawal interval recommendation is limited to plasma pharmacokinetic data and minimal milk residue data that is limited to cattle. Therefore, a rapid residue detection test (RRDT) could be a useful resource to determine if milk samples are free of drug residues and acceptable for sale. This study compared a commercially available RRDT (Charm® FLT strips) to detect florfenicol residues in fresh milk samples from healthy adult dairy breed goats treated with florfenicol (40 mg/kg subcutaneously twice 4 days apart) with quantitative analysis of florfenicol concentrations using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). In addition, storage claims for testing bovine milk using the RRDT were assessed using stored goat milk samples. Milk samples were collected every 12 h for a minimum of 26 days. Commercial RRDT strips remained positive in individual goats ranging from 528 to 792 h (22-33 days) after the second dose, whereas, UPLC-MS/MS indicated the last detectable florfenicol concentration in milk samples ranged from 504 to 720 h (21-30 days) after the second dose. Results from stored milk samples from treated goats indicate that samples can be stored for up to 5 days in the refrigerator and 60 days in the freezer after milking prior to being tested with a low risk of false-negative test results due to drug degradation. Elevated somatic cell counts and bacterial colony were noted in some of the milk samples in this study, but further study is required to understand the impact of these quality factors on RRDT results.

Residue depletion profiles and withdrawal interval estimations of meloxicam in eggs and ovarian follicles following intravenous (Meloxicam solution for injection) and oral (Meloxidyl®) administration in domestic chickens (Gallus domesticus).

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) commonly prescribed in an extralabel manner for treating chickens in urbanized settings. The objectives of this study were to determine meloxicam depletion profiles in eggs and ovarian follicles and to estimate associated withdrawal intervals (WDI) in laying hens following a single intravenous or repeated oral administration. The observed peak concentration of meloxicam in ovarian follicles were consistently higher than in egg yolk and egg white samples. Terminal half-lives were 31-h, 113-h and 12-h in ovarian follicles, egg yolk and egg white samples, respectively, for repeated oral administrations at 1 mg/kg for 20 doses at 12-h intervals. The terminal half-life following a single intravenous administration at 1 mg/kg was 50-h for ovarian follicles. Meloxicam WDI estimations using ovarian follicle and egg yolk concentration data following 20 doses at 12-h intervals were 36 and 12 days, respectively. Meloxicam WDI estimation using egg yolk concentration data following 8 doses at 24-h intervals was 12 days. These results improve our understanding on the residue depletion of meloxicam from chickens' reproductive tracts and egg products and provide WDIs to help ensure food safety for humans consuming eggs from treated laying hens.

Pharmacokinetic Parameters and Estimating Extra-Label Tissue Withdrawal Intervals Using Three Approaches and Various Matrices for Domestic Laying Chickens Following Meloxicam Administration.

Meloxicam is commonly prescribed for treating chickens in backyard or small commercial operations despite a paucity of scientific data establishing tissue withdrawal interval recommendations following extra-label drug use (ELDU). Historically, ELDU withdrawal intervals (WDIs) following meloxicam administration to chickens have been based on the time when meloxicam concentrations fall below detectable concentrations in plasma and egg samples. To date, no studies have addressed tissue residues. ELDU WDIs are commonly calculated using terminal elimination half-lives derived from pharmacokinetic studies. This study estimated pharmacokinetic parameters for laying hens following meloxicam administration and compared ELDU WDIs calculated using tissue terminal elimination half-lives vs. those calculated using FDA tolerance and EMA's maximum regulatory limit statistical methods, respectively. In addition, ELDU WDIs were calculated using plasma meloxicam concentrations from live birds to determine if plasma data could be used as a proxy for estimating tissue WDIs. Healthy domestic hens were administered meloxicam at 1 mg/kg intravenous (IV) once, 1 mg/kg orally (PO) once daily for eight doses or 1 mg/kg PO twice daily for 20 doses. Analytical method validation was performed and meloxicam concentrations were quantified using high-performance liquid chromatography. In general, the terminal elimination technique resulted in the longest ELDU WDIs, followed by the FDA tolerance and then EMA's maximum residue limit methods. The longest ELDU WDIs were 72, 96, and 384 (or 120 excluding fat) h for the IV, PO once daily for eight doses, and PO twice daily for 20 doses, respectively. Plasma data are a possible dataset for estimating a baseline for tissue ELDU WDI estimations when tissue data are not available for chickens treated with meloxicam. Finally, pharmacokinetic parameters were similar in laying hens to those published for other avian species.

Pharmacokinetic Parameters and Tissue Withdrawal Intervals for Sheep Administered Multiple Oral Doses of Meloxicam.

Meloxicam is an anti-inflammatory drug used to treat pain and inflammation in ruminants including sheep, and pharmacokinetic studies are needed to protect the food supply from drug residues after use in food-producing animals. This study estimated plasma pharmacokinetic parameters and meat withdrawal intervals (WDI) for market sheep after multiple daily oral doses of meloxicam. Single and multiple dose plasma pharmacokinetic studies, a multi-dose tissue depletion study, and a follow-up study to investigate if events prior to slaughter were associated with differences in plasma meloxicam concentrations, all using sample data collected after completion of dosing, were completed. Using regulatory agency methods for calculating withdrawal times, an estimated WDI of at least 10 d following the last dose is recommended for market lambs treated with 10 daily oral 1 mg/kg doses of meloxicam tablets suspended in water. The effect of events surrounding slaughter on plasma meloxicam concentrations in lambs is unknown but should be considered if plasma samples are obtained immediately prior to or during the slaughter process and used for pharmacokinetic investigations.

Drug residues in poultry meat: A literature review of commonly used veterinary antibacterials and anthelmintics used in poultry.

Poultry meat is widely consumed throughout the world and production practices often include the administration of pharmaceutical products. When appropriate, extra-label drug use of medications is necessary, but scientifically derived drug withdrawal intervals must be observed so that poultry meat is not contaminated with drug residues which could pose health risks to consumers. Over the past decade, there has been increased advocacy for judicious use of antimicrobial drugs for treating food animals. Judicious use of medications is commonly referred to as practices that reduce antibiotic resistance, but also includes residue avoidance. In that light, many investigators have performed scientific studies and have published estimated pharmacokinetic parameters for veterinary medications used in commercial avian species. This manuscript is a review of medication classes that have been studied in poultry (mostly chickens) with an emphasis on drug residue depletion in poultry meat.