title: Plasma disposition and faecal excretion of eprinomectin following topical and subcutaneous administration in non-lactating dairy cattle.
abstract: OBJECTIVE
  To investigate the plasma disposition and faecal excretion of eprinomectin (EPM) in non-lactating dairy cattle following topical and S/C administration.
  
  
  METHODS
  Holstein dairy cows, 3.5-5 years-old, were selected 20-25 days after being dried off and were randomly allocated to receive EPM either topically (n=5) or S/C (n=5) at dose rates of 0.5 and 0.2 mg/kg bodyweight, respectively. Heparinised blood and faecal samples were collected at various times between 1 hour and 30 days after treatment, and were analysed for concentrations of EPM using high performance liquid chromatography with a fluorescence detector.
  
  
  RESULTS
  The maximum concentration of EPM in plasma (Cmax) and the time to reach Cmax were both greater after S/C administration (59.70 (SD 12.90) ng/mL and 1.30 (SD 0.27) days, respectively) than after topical administration (20.73 (SD 4.04) ng/mL and 4.40 (SD 0.89) days, respectively) (p<0.001). In addition, S/C administration resulted in greater plasma availability (area under the curve; AUC), and a shorter terminal half-life and mean residence time (295.9 (SD 61.47) ng.day/mL; 2.95 (SD 0.74) days and 4.69 (SD 1.01) days, respectively) compared with topical administration (168.2 (SD15.67) ng.day/mL; 4.63 (SD 0.32) days, and 8.23 (SD 0.57) days, respectively) (p<0.01). EPM was detected in faeces between 0.80 (SD 0.45) and 13.6 (SD 4.16) days following S/C administration, and between 1 (SD 0.5) and 20.0 (SD 3.54) days following topical administration. Subcutaneous administration resulted in greater faecal excretion than topical administration, expressed as AUC adjusted for dose (1188.9 (SD 491.64) vs. 311.5 (SD 46.90) ng.day/g; p<0.05). Maximum concentration in faeces was also higher following S/C than topical administration (223.0 (SD 63.96) vs. 99.47 (SD 43.24) ng/g; p<0.01).
  
  
  CONCLUSIONS
  Subcutaneous administration of EPM generated higher plasma concentrations and greater plasma availability compared with topical administration in non-lactating cattle. Although the S/C route provides higher faecal concentrations, the longer faecal persistence of EPM following topical administration may result in more persistent efficacy preventing establishment of incoming nematode larvae in cattle.
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Veterinary , Balikesir University , Balikesir , Turkey.
authors.forename: D
authors.initials: D
authors.lastname: Aksit
authors.affiliation: b Department of Medical Pharmacology, Faculty of Medicine , Balikesir University , Balikesir , Turkey.
authors.forename: O
authors.initials: O
authors.lastname: Korkut
authors.affiliation: b Department of Medical Pharmacology, Faculty of Medicine , Balikesir University , Balikesir , Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Aksoz
authors.affiliation: b Department of Medical Pharmacology, Faculty of Medicine , Balikesir University , Balikesir , Turkey.
authors.forename: C
authors.initials: C
authors.lastname: Gokbulut
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002417:Cattle; D005243:Feces / Q000737:chemistry*; D005260:Female; D006207:Half-Life; D007559:Ivermectin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D065566:Subcutaneous Absorption
chemical_list: D000871:Anthelmintics; D007559:Ivermectin; C101434:eprinomectin
keywords: Eprinomectin; dairy cattle; ecotoxicity; endectocides; faeces; macrocyclic lactones; pharmacokinetics; pour-on