title: Concentrations of buparvaquone in milk and tissue of dairy cows.
abstract: OBJECTIVE
  To determine the concentration of the anti-theilerial drug buparvaquone in the milk and tissue of dairy cattle following treatment with two different formulations, and to assess the effect of clinical theileriosis on the concentration of buparvaquone in milk.
  
  
  METHODS
  Healthy lactating dairy cows (n=25) were injected once (Day 0) I/M with 2.5 mg/kg of one of two formulations of buparvaquone (Butalex; n=12 or Bupaject; n=13). Milk samples were collected from all cows daily until Day 35. Five cows were slaughtered on each of Days 56, 119, 147, 203 and 328, and samples of liver, muscle and injection site tissue collected. Milk samples were also collected from cows (n=14) clinically affected with theileriosis for up to 21 days after treatment with buparvaquone. Milk and tissue samples were analysed by liquid chromatography-mass spectrometry; limits of detection (LOD) were 0.00018 mg/kg for muscle and 0.00023 mg/L for milk. Concentrations of buparvaquone in milk and tissues were log10-transformed for analysis using multivariate models.
  
  
  RESULTS
  In healthy cows, concentrations of buparvaquone in milk declined with time post-treatment (p<0.001), but were above the LOD in 11 of 25 cows at Day 35. Concentration in milk was higher one day after treatment in cows treated with Butalex than in cows treated with Bupaject, but not different thereafter (p=0.007). Concentrations of buparvaquone in muscle were below the LOD for four of five animals at Day 119 and for all animals by Day 147, but were above the LOD at the injection site of one cow, and in the liver of three cows at Day 328. Tissue concentrations did not differ with formulation nor was there a formulation by time interaction (p>0.3). Concentrations of buparvaquone in the milk of clinically affected animals were not different from those of healthy animals at 1 and 21 days post-treatment (p=0.72). Between 21 and 25 days post-treatment concentrations were below the LOD in 9/14 milk samples from clinically affected cows.
  
  
  CONCLUSIONS
  Detectable concentrations of buparvaquone were found in the milk of some cows for at least 35 days and in the liver and injection site of some cows until at least 328 days after injection. There were no biologically meaningful differences in milk or tissue concentrations between the formulations, or in the milk concentrations for cows that were clinically affected compared with those that were healthy at the time of treatment.
authors.affiliation: a Cognosco , AnexaFVC , PO Box 21, Morrinsville 3340 , New Zealand.
authors.forename: S
authors.initials: S
authors.lastname: McDougall
authors.affiliation: b DairyNZ Ltd , Private Bag No. 3221, Hamilton 3240 , New Zealand.
authors.forename: J E
authors.initials: JE
authors.lastname: Hillerton
authors.affiliation: c Fonterra Co-operative Group , Private Bag 92032, Auckland 1010 , New Zealand.
authors.forename: D
authors.initials: D
authors.lastname: Pegram
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000032:analysis* / Q000627:therapeutic use; D002417:Cattle; D005260:Female; D007273:Injections, Intramuscular / Q000662:veterinary; D008099:Liver / Q000737:chemistry; D008892:Milk / Q000737:chemistry*; D018482:Muscle, Skeletal / Q000737:chemistry; D009285:Naphthoquinones / Q000008:administration & dosage / Q000032:analysis* / Q000627:therapeutic use; D013801:Theileriasis / Q000188:drug therapy
chemical_list: D000981:Antiprotozoal Agents; D009285:Naphthoquinones; C046326:buparvaquone
keywords: Theileria; buparvaquone; dairy cattle; liver; milk