11 Determination of Milk Concentrations and Pharmacokinetics of Salicylic Acid Following Acetylsalicylic Acid (Aspirin) Administration in Postpartum Dairy Cows

Abstract

Abstract Administration of non-steroidal anti-inflammatory drugs, such as the widely available drug aspirin, or acetylsalicylic acid (ASA), may improve health and milk production in postpartum dairy cows. However, plasma pharmacokinetic (PK) data for salicylic acid (SA), the active metabolite of ASA, are unrepresentative of lactating dairy cows and current treatment regimens, and there are currently no published milk residue and minimal pharmacodynamic data available for ASA or SA in dairy cows. The objectives of this descriptive study were to (1) describe the pharmacokinetics of SA in the milk and plasma of postpartum dairy cows following oral ASA administration; (2) to estimate a milk withdrawal period for dairy cows treated with ASA; and (3) to determine the impact of ASA on plasma prostaglandin E2 metabolite (PGEM) concentrations. Primiparous (n = 3) and multiparous (n = 7) postpartum Holstein dairy cows received 2 oral treatments with ASA at 200 mg/kg, 24 h apart. Plasma and milk SA concentrations from 0 h through 120 h after ASA administration were analyzed using ultra-performance liquid chromatography triple quadrupole mass spectrometry. Plasma PK analysis was performed using a non-compartmental approach using the free software, PKSolver, in Excel. An estimated milk withdrawal interval of 168 h was determined using the FDA Milk Discard App in R (RStudio, Boston, MA) using a 99th percentile upper tolerance limit with 95% confidence. Plasma PGEM concentrations from 0 h to 24 h after ASA administration were determined in duplicate using ELISA and were reduced compared with baseline for up to 12 h after ASA administration. A mean reduction in PGEM of -49.3% was observed at 2 h. Results from this study suggest that the current milk withhold recommendation of 24 h for dairy cows administered ASA should be revised and that ASA administration may mitigate postpartum inflammation through reduction in prostaglandin production.