title: The impact of the site of blood sampling on pharmacokinetic parameters following sublingual dosing to dogs.
abstract: BACKGROUND
  Drugs are most commonly administered orally, but some potential drug candidates are not suited for oral administration due to poor absorption, high first pass metabolism or gastrointestinal side effects. The interest for transmucosal dosing for systemic drug delivery is increasing, e.g. buccal, sublingual and nasal routes. The evaluation of the systemic plasma concentration and the derivation of the pharmacokinetic parameters of candidate compounds in preclinical studies are essential for drug development. The effect of site of blood sampling on the measured drug concentration, in both animals and humans, is to some extent known but it is not always taken into consideration in the design of pharmacological and toxicological studies.
  
  
  METHODS
  Blood samples were collected both from leg and jugular veins from beagle dogs following a single sublingual dosing of Compound A in order to determine the impact of different sites of blood sampling on plasma pharmacokinetics. Plasma was prepared by centrifugation and plasma concentrations of Compound A were determined by protein precipitation and liquid chromatography followed by mass spectrometric detection. The pharmacokinetic parameters were calculated by non-compartment methods.
  
  
  RESULTS
  Sampling from the jugular vein resulted in higher and more variable exposure during the absorption phase compared to sampling from a leg vein. The plasma exposure in the jugular vein, in terms of C(max), was 4-fold compared to that in the leg vein and an approximately 2-fold bioavailability was observed.
  
  
  CONCLUSIONS
  The aim of this investigation was to determine the impact of the different sites of blood sampling on assessing systemic plasma exposure and pharmacokinetic parameters for Compound A following sublingual dosing to dogs. The results demonstrate the significant impact that the site of blood sampling has on PK parameters, and raise concerns of using the jugular vein as a site of sampling after sublingual and other transmucosal routes of dosing in the head region.
authors.affiliation: Innovative Medicines CNS&Pain, DMPK, AstraZeneca R&D, SE-151 85 Södertälje, Sweden. elin.sohlberg@gmail.com
authors.forename: E
authors.initials: E
authors.lastname: Sohlberg
authors.forename: M M
authors.initials: MM
authors.lastname: Halldin
authors.forename: A
authors.initials: A
authors.lastname: Annas
authors.forename: K
authors.initials: K
authors.lastname: Königsson
authors.forename: B
authors.initials: B
authors.lastname: Jansson
authors.forename: R
authors.initials: R
authors.lastname: Pehrson
authors.forename: N
authors.initials: N
authors.lastname: Borg
mesh_terms: D000286:Administration, Sublingual; D000818:Animals; D001682:Biological Availability; D001800:Blood Specimen Collection / Q000379:methods*; D004285:Dogs; D005121:Extremities / Q000098:blood supply*; D005260:Female; D007601:Jugular Veins / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000097:blood*
chemical_list: D004364:Pharmaceutical Preparations