title: Clinical validation of dried blood spot sampling in therapeutic drug monitoring of ciclosporin A in allogeneic stem cell transplant recipients: direct comparison between capillary and venous sampling.
abstract: BACKGROUND
  The immunosuppressive drug ciclosporin A has a narrow therapeutic window and a large inter- and intraindividual pharmacokinetic variability. Therapeutic drug monitoring of ciclosporin is usually performed in ethylenediaminetetraacetic acid blood, obtained by venous sampling. Dried blood spot sampling (DBS) could be a useful alternative sampling method, which also easily allows multiple sampling, for example, for obtaining area under the curve. With DBS, capillary blood is obtained from a finger prick with an automatic lancet by the patients themselves, and the drop of blood is applied to sampling paper. This may limit the number and duration of hospital visits for these patients.
  
  
  METHODS
  We describe a validation study in which venous and finger prick blood samples were collected at the same time. Venous sampling was performed by venipuncture, and the ethylenediaminetetraacetic acid blood samples were collected and stored at 4°C until analysis. Finger prick blood samples were collected using an automatic lancing device. The volume of the blood drops of patients was approximately 30 μL, and blood spots of about 10-mm diameter were produced. Paper disks with a diameter of 8 mm were punched out with an electromagnetic-driven hole puncher. DBS was compared with the routine assay in venous blood. The study population consisted of adult patients (18 years or older) who were treated with ciclosporin A and routinely monitored for adequate blood concentrations.
  
  
  RESULTS
  Thirty-eight duplicate dried blood spots and venous samples were studied. Using weighted Deming regression, the slope was 1.01 with a standard error of 0.03 associated with an intercept of -9.0 (standard error = 5.9). These results indicate that there is no significant difference between the 2 sampling methods. For the medical decision level of 300 mcg/L, the bias was -4.7 mcg/L with a 95% confidence interval of -19.2 to 9.8 mcg/L. The Altman-Bland plot showed no difference between the 2 sampling methods.
  
  
  CONCLUSIONS
  Our results demonstrate that DBS is a valid alternative for conventional venous sampling in allogeneic stem cell transplant recipients.
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands. aj.wilhelm@vumc.nl
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Wilhelm
authors.forename: Adinda
authors.initials: A
authors.lastname: Klijn
authors.forename: Jeroen C G
authors.initials: JC
authors.lastname: den Burger
authors.forename: Otto J
authors.initials: OJ
authors.lastname: Visser
authors.forename: Agnes I
authors.initials: AI
authors.lastname: Veldkamp
authors.forename: Jeroen J W M
authors.initials: JJ
authors.lastname: Janssen
authors.forename: Eleonora L
authors.initials: EL
authors.lastname: Swart
mesh_terms: D000293:Adolescent; D002196:Capillaries / Q000737:chemistry*; D016572:Cyclosporine / Q000097:blood* / Q000627:therapeutic use*; D059788:Dried Blood Spot Testing / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D004492:Edetic Acid / Q000737:chemistry; D005385:Fingers / Q000098:blood supply; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000627:therapeutic use; D018962:Phlebotomy / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods; D014180:Transplantation; D014184:Transplantation, Homologous / Q000379:methods; D014680:Veins / Q000737:chemistry*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D004492:Edetic Acid