title: Clinical Application of the Dried Blood Spot Method in the Measurement of Blood Busulfan Concentration.
abstract: The dried blood spot (DBS) method, which is a simple technique for blood sample processing involving the placement of a drop of whole blood onto filter paper, has been used recently in clinical pharmacology to determine blood concentrations of various drugs. This study examined the feasibility of the clinical application of the DBS method for individual busulfan dose adjustments. Pharmacokinetic (PK) parameters of blood samples for busulfan measurements determined using the DBS method were compared with those using plasma separation (the conventional method). Blood samples were collected from patients receiving i.v. busulfan as a conditioning regimen before allogeneic hematopoietic stem cell transplantation at Toranomon Hospital, Japan. Samples collected 2, 4, and 6 hours after the start of the first drip infusion were processed by DBS or the conventional method. The area under the blood concentration-time curve (AUC) and other PK parameters were calculated to compare the 2 methods. Divergence of <20% in each parameter was considered acceptable. The divergence range for each parameter was as follows: blood concentration at 2 hours after the start of drip infusion, .6 to 8.2%; at 4 hours, .3 to 10.0%; at 6 hours, .3 to 14.2%; and AUC0-∞, .0 to 10.3%. None of the PK parameters showed a divergence between the DBS method and the conventional method exceeding 20%, suggesting that both methods are well correlated. The clinical application of blood sample processing with the DBS method in the measurement of blood busulfan concentration may therefore be feasible, but further studies are needed to confirm these findings.
authors.affiliation: Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto, Japan. Electronic address: kmatsumo@dwc.doshisha.ac.jp.
authors.forename: Kana
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Uchida
authors.affiliation: Pharmacokinetics Research Laboratories, Toray Research Center, Inc., Tokyo, Japan.
authors.forename: Amane
authors.initials: A
authors.lastname: Sakurai
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Taniguchi
authors.affiliation: Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Morita
mesh_terms: D000328:Adult; D000368:Aged; D001800:Blood Specimen Collection; D002066:Busulfan / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D059788:Dried Blood Spot Testing / Q000379:methods*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: D019653:Myeloablative Agonists; D002066:Busulfan
keywords: Busulfan; Dried blood spot; Pharmacokinetics; Therapeutic drug monitoring