title: Pharmacokinetics for once-daily modified release formulation of tacrolimus hydrate in unrelated hematopoietic stem cell transplantation.
abstract: A once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed in response to the problem of nonadherence. However, there have been no data available about the efficacy of Tac QD conversion from intravenous Tac (Tac i.v.) in allogeneic hematopoietic stem cell transplantation (allo-SCT). We analyzed the pharmacokinetics (PK) of Tac QD in allo-SCT recipients. A total of 10 patients with hematological malignancies who received allo-SCT from unrelated donors were enrolled. Patients received Tac i.v. at 0.03 mg/kg a day before transplantation. Administration of Tac i.v. was converted to Tac QD at a 1:4 ratio when the patients had recovered from regimen-related gastrointestinal toxicity and could tolerate oral medication. After conversion, six out of 10 patients (60 %) showed a sustained decrease in Tac exposure and required dose adjustment. The conversion from Tac i.v. to Tac QD should be performed under close medical supervision. Area under the curve (AUC) and the trough of Tac QD showed a correlation, and the trough should be maintained above 7.5 ng/ml to provide an adequate AUC. Although four patients received bone marrow from an HLA DRB1 1 antigen-mismatched unrelated donor, no patients developed grade III-IV acute graft-versus-host disease (GVHD). The modification of Tac QD to maintain a whole-blood trough concentration above 7.5 ng/ml may be as effective as Tac BID.
authors.affiliation: Division of Clinical Oncology and Hematology, Jikei University School of Medicine, 3-25-8 Nishi Shinbashi, Minatoku, Tokyo, 105-8461, Japan, yano@jikei.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Yano
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Mori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Tomohito
authors.initials: T
authors.lastname: Machishima
authors.forename: Takaki
authors.initials: T
authors.lastname: Shimada
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yahagi
authors.forename: Katsuki
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ogasawara
authors.forename: Shinobu
authors.initials: S
authors.lastname: Takahara
authors.forename: Kinuyo
authors.initials: K
authors.lastname: Kasama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Katsube
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kamiyama
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Inui
authors.forename: Noriko
authors.initials: N
authors.lastname: Usui
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aiba
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007938:Leukemia / Q000378:metabolism / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000628:therapy; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus