title: Effect of cimetidine on pharmacokinetics of orally administered cyclosporine in healthy dogs.
abstract: OBJECTIVE
  To describe the pharmacokinetics of cyclosporine (CyA) in healthy dogs after oral administration alone or in combination with orally administered cimetidine.
  
  
  METHODS
  10 healthy adult Beagles.
  
  
  METHODS
  Dogs were randomly assigned to receive CyA alone or CyA in combination with cimetidine. After a washout period of 2 weeks, dogs then received the alternate treatment. The CyA plus cimetidine treatment required administration of cimetidine (15 mg/kg of body weight, PO, q 8 h) for 8 days and administration of CyA (5 mg/kg, PO, q 24 h) on days 6 through 8. The CyA treatment alone required administration of CyA (5 mg/kg, PO, q 24 h) for 3 days. On the third day of CyA administration during each treatment, blood samples were collected immediately before (time 0) and 0.5, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 11, 13, 15, 21, and 24 hours after initiating CyA administration.
  
  
  RESULTS
  Time until maximum CyA concentration was significantly longer for CyA in combination with cimetidine. Assessment of estimated pharmacokinetic variables revealed a significantly faster rate of change in the distribution phase for CyA in combination with cimetidine. Maximum CyA concentration differed significantly among dogs but did not differ significantly between treatments.
  
  
  CONCLUSIONS
  Analysis of our data suggests that cimetidine may affect absorption of orally administered CyA, but overall, it does not affect the pharmacokinetics of CyA. There is considerable variability in the maximum concentration of CyA among dogs, and monitoring of blood concentrations of CyA during treatment is advised.
authors.affiliation: Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Daigle
authors.forename: G
authors.initials: G
authors.lastname: Hosgood
authors.forename: C S
authors.initials: CS
authors.lastname: Foil
authors.forename: R P
authors.initials: RP
authors.lastname: Hunter
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002927:Cimetidine / Q000494:pharmacology*; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000819:agonists / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000819:agonists / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D011897:Random Allocation
chemical_list: D006635:Histamine H2 Antagonists; D007166:Immunosuppressive Agents; D002927:Cimetidine; D016572:Cyclosporine