title: New model for intravenous drug administration and blood sampling in the awake rat, designed to increase quality and throughput for in vivo pharmacokinetic analysis.
abstract: BACKGROUND
  There is a continuing need for increased throughput in the examination of new chemical entities (NCEs) in terms of the pharmacokinetic (PK) parameters. The aim was to validate a new study method designed to improve throughput and reduce inter-animal variability and animal number requirement in routine bioavailability and plasma PK studies of NCEs in awake rats.
  
  
  METHODS
  The design uses a new method for intravenous (iv) administration via the saphenous vein in combination with serial blood sampling via the tail vein. The multiple sampling method was compared with single sampling (decapitation) and the effect on haematocrit (Hct) levels was studied. Direct injection in the saphenous vein was compared to iv administration using an indwelling jugular catheter.
  
  
  RESULTS
  Using structurally different NCEs, it was shown that a combination of direct injection via the saphenous vein and multiple sampling from the tail vein produces comparable plasma concentrations and subsequent PK results to the comparator methods. Furthermore, Hct levels remained within recommended levels using a total blood sampling volume of up to 2.1 ml/day for rats with a body weight of around 250 g.
  
  
  CONCLUSIONS
  The new model increases throughput by avoiding the time required for preparative surgery, increases quality by allowing inter-animal comparison of major PK parameters as concentration time curves can be obtained from each animal, and reduces the number of animals required.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, Division of Janssen Pharmaceutica N.V., Discovery ADME-Tox, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Claire
authors.initials: C
authors.lastname: Mackie
authors.forename: Koen
authors.initials: K
authors.lastname: Wuyts
authors.forename: Marc
authors.initials: M
authors.lastname: Haseldonckx
authors.forename: Saskia
authors.initials: S
authors.lastname: Blokland
authors.forename: Petra
authors.initials: P
authors.lastname: Gysemberg
authors.forename: Iris
authors.initials: I
authors.lastname: Verhoeven
authors.forename: Philip
authors.initials: P
authors.lastname: Timmerman
authors.forename: Marjoleen
authors.initials: M
authors.lastname: Nijsen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001800:Blood Specimen Collection / Q000379:methods*; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D006207:Half-Life; D006400:Hematocrit / Q000379:methods; D007275:Injections, Intravenous / Q000379:methods; D007601:Jugular Veins; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012501:Saphenous Vein
chemical_list: D015507:Drugs, Investigational