Pharmacokinetics of ketamine and lidocaine in serum and milk of mature Holstein cows.

Abstract

Ketamine and lidocaine are two commonly used anesthetics in veterinary medicine, with some animals occasionally being sent for slaughter following drug administration. The United States Department of Agriculture (USDA) and Food and Drug Administration (FDA) have a stern tolerance policy for drug residues in meat and milk. The objectives of this study were to investigate the pharmacokinetics of ketamine following administration of a single intravenous dose (5 milligrams per kilogram) and lidocaine administered via inverted L (100 milliliters total) and caudal epidural nerve blocks (0.22 milligrams per kilogram) and to utilize the information to recommend and help guide withdrawal times for meat and milk of these two anesthetics in mature Holstein cows. Ketamine and 2% lidocaine were administered to nine healthy, mature, lactating Holstein cows with a 14 day washout period between the three treatments. Serum samples were collected over 24 hours and milk samples were collected over 60 hours following drug administration. Samples were analyzed using a High Performance Liquid Chromatographic system and a standard curve linear equation was calculated for both drugs. Statistical analysis and pharmacokinetic parameters of ketamine and lidocaine were calculated using non-compartmental methods. Ketamine administered intravenously as a single anesthetic dose of 5 milligrams per kilogram was detected from 0.083 to 8.0 hours in serum and from 0.5 to 48 hours in milk. The longest elimination half-life of ketamine in serum was approximately 3 hours (1.41 to 2.78 hours, mean 1.80 ± 0.50 hours). Calculating for safety, the meat withdrawal time is recommended as 30 hours or approximately 2 days. The last detectable ketamine concentration in milk was 48 hours with no residue detected at 60 hours (36 to 48 hours, mean 46 ± 4.90). Therefore, a milk withdrawal time of approximately 72 hours or approximately 3 days is recommended. Lidocaine administered as an inverted L nerve block using a volume of 100 milliliters was detected in serum from 0.083 to 10 hours and in milk from 0.5 to 48 hours. The longest elimination half-life of lidocaine in the serum was approximately 8 hours (2.1 to 7.26 hours, mean 4.19 ± 1.69). Calculating for safety, the meat withdrawal time is recommended as 80 hours or approximately 4 days. The last detectable lidocaine concentration in milk was 48 hours with no residue detected at 60 hours (8 to 48 hours, mean 32.5 ± 16.2). Therefore, a milk withdrawal time of approximately 72 hours or approximately 3 days is recommended. There was no detectable lidocaine concentration in the milk or serum samples at any time following caudal epidural administration at a dose of 0.22 milligrams per kilogram. Therefore this anesthetic technique may be performed without the potential for meat or milk contamination.