title: Pharmacokinetics of cyclophosphamide after oral and intravenous administration to dogs with lymphoma.
abstract: BACKGROUND
  Cyclophosphamide is an alkylating chemotherapeutic drug administered i.v. or p.o.. It is currently assumed that exposure to the active metabolite, 4-hydroxycyclophosphamide (4-OHCP), is the same with either route of administration.
  
  
  OBJECTIVE
  To characterize the pharmacokinetics of cyclophosphamide and 4-OHCP in dogs with lymphoma when administered p.o. or i.v..
  
  
  METHODS
  Sixteen client-owned dogs with substage A lymphoma were enrolled in the study. Eight dogs received cyclophosphamide i.v. and 8 received it p.o..
  
  
  METHODS
  Prospective randomized clinical trial was performed. Blood was collected from each dog at specific time points after administration of cyclophosphamide. The serum was evaluated for the concentration of cyclophosphamide and 4-OHCP with mass spectrometry and liquid chromatography.
  
  
  RESULTS
  Drug exposure to cyclophosphamide measured by area under the curve (AUC)(0-inf) is significantly higher after intravenous administration (7.14 ± 3.77 μg/h/mL) compared with exposure after oral administration (P-value < .05). No difference in drug exposure to 4-OHCP was detected after i.v. (1.66 ± 0.36 μg/h/mL) or p.o. (1.42 ± 0.64 μg/h/mL) administered cyclophosphamide.
  
  
  CONCLUSIONS
  Drug exposure to the active metabolite 4-OHCP is equivalent after administration of cyclophosphamide either p.o. or i.v..
authors.affiliation: Animal Cancer Center, Colorado State University, Fort Collins, CO 80523-1620, USA. emwarry@colostate.edu
authors.forename: E
authors.initials: E
authors.lastname: Warry
authors.forename: R J
authors.initials: RJ
authors.lastname: Hansen
authors.forename: D L
authors.initials: DL
authors.lastname: Gustafson
authors.forename: S E
authors.initials: SE
authors.lastname: Lana
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D004283:Dog Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D006207:Half-Life; D007262:Infusions, Intravenous / Q000662:veterinary; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D011446:Prospective Studies; D011897:Random Allocation; D021241:Spectrometry, Mass, Electrospray Ionization; D018709:Statistics, Nonparametric
chemical_list: C012358:4-hydroxycyclophosphamide; D003520:Cyclophosphamide