title: A study to examine the relationship between metritis severity and depletion of oxytetracycline in plasma and milk after intrauterine infusion.
abstract: Metritis is a frequent problem in postpartum dairy cows. Intrauterine therapy with the antimicrobial oxytetracycline (OTC) is often used, although this therapy has not been shown to be superior to systemic therapy. The objectives of this study were to (1) determine the plasma and milk concentrations of OTC following intrauterine infusion in postpartum dairy cows with varying degrees of metritis severity; (2) determine the depletion time of OTC in an attempt to provide veterinarians withdrawal guidelines, should they use this therapy; and (3) correlate metritis severity scores with OTC concentrations in plasma and milk. Our hypothesis was that cows with more severe metritis would have higher OTC concentrations in milk following intrauterine therapy. Thirty-two cows were selected to participate in the study after farm personnel had determined that they had metritis based on evaluation of vaginal discharge between 4 and 14 DIM, in accordance with the farm's treatment protocols. Metritis scores (1-4) were assigned based on a published scheme: 1 represented yellow-to-orange thick discharge or translucent mucus with no fetid smell; 2 represented blood-tinged vaginal mucus, slightly watery, with little or no fetid smell; 3 represented red to red/brown watery discharge with moderate fetid smell; and 4 represented red to red/brown watery discharge containing pieces of placenta and an intense fetid smell. Trial cows received a single treatment of 4g of OTC (approximately 6.7mg/kg) via intrauterine infusion. Blood samples were collected over 96h, and milk samples were collected before intrauterine therapy and 3 times a day for 4 d following infusion. Following treatment, OTC rapidly diffused to plasma and subsequently to milk. Maximum OTC concentrations in plasma and milk occurred within the first 24h following intrauterine infusion, and 25 of the 32 cows had detectable OTC concentrations in milk at 4 d after intrauterine infusion. Cows with clinical metritis (metritis severity scores of 3 or 4) at the initiation of treatment were significantly and positively correlated with higher milk OTC concentrations at the second [time (T)9 h; r=0.43], fourth (T25 h; r=0.42), and fifth milking following treatment (T33 h; r=0.38) compared with cows with normal vaginal discharge. We also observed a positive correlation between initial metritis score and milk maximum concentration (r=0.36) and milk area under the concentration curve (r=0.36). Given that intrauterine administration of OTC is an extra-label therapy, dairy producers should consult with their veterinarian to ensure that milk is being tested at or below the established tolerance for OTC. This will ensure that violative drug residues do not enter the human food supply.
authors: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames 50011. Electronic address: pgorden@iastate.edu.
authors: P J
authors: PJ
authors: Gorden
authors: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames 50011.
authors: J A
authors: JA
authors: Ydstie
authors: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames 50011.
authors: M D
authors: MD
authors: Kleinhenz
authors: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames 50011; Pharmacology Analytical Support Team, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Iowa State University, Ames 50011.
authors: L W
authors: LW
authors: Wulf
authors: Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan 66502.
authors: R
authors: R
authors: Gehring
authors: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames 50011; Pharmacology Analytical Support Team, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Iowa State University, Ames 50011.
authors: C J
authors: CJ
authors: Lee
authors: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames 50011.
authors: C
authors: C
authors: Wang
authors: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames 50011; Pharmacology Analytical Support Team, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Iowa State University, Ames 50011. Electronic address: hcoetzee@iastate.edu.
authors: J F
authors: JF
authors: Coetzee
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy; D004716:Endometritis / Q000662:veterinary; D005260:Female; D006801:Humans; D008892:Milk / Q000737:chemistry*; D010118:Oxytetracycline / Q000378:metabolism* / Q000627:therapeutic use*; D049590:Postpartum Period
chemical_list: D010118:Oxytetracycline
keywords: bovine metritis; drug residues; oxytetracycline; pharmacokinetics