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Pharmacokinetics of cyclosporine A at a high‐peak concentration of twice‐daily infusion and oral administration in allogeneic haematopoietic stem cell transplantation
Author(s) -
Inoue Y.,
Saito T.,
Ogawa K.,
Nishio Y.,
Kosugi S.,
Suzuki Y.,
Shibuya Y.,
Kato M.,
Takahashi M.,
Miura I.
Publication year - 2011
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2010.01199.x
Subject(s) - pharmacokinetics , medicine , oral administration , dosing , transplantation , calcineurin , pharmacology , trough level , hematopoietic stem cell transplantation , trough concentration , area under the curve , urology , tacrolimus
Summary What is known and Objective: The most appropriate immunosuppressive strategy with calcineurin inhibitors for the prevention of acute graft‐versus‐host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT) has not yet been established. To estimate the safety and efficacy of a new strategy, we investigated the pharmacokinetics of cyclosporine A (CyA) delivered by twice‐daily infusion and oral administration maintained with a peak level above 1000 ng/mL to keep 24 h area under the concentration–time curve (AUC0–24) higher than 10 000 ng·h/mL in 12 patients. Methods: Cyclosporine A was started as a twice‐daily infusion at 1·5 mg/kg and then orally administered at twice the infusion dose to maintain the trough blood concentration between 200 and 500 ng/mL, and with a peak level above 1000 ng/mL. Serial blood samples were collected at 0, 1, 2, 3, 5, 8 and 12 h after CyA dosing (C0, C1, C2, C3, C5, C8 and C12) on days 14–21 after transplantation and on days 7–14 after switching to oral administration, and the AUC was calculated. Results: In all patients, the AUC0–24 for both twice‐daily infusion and oral administration was higher than 10 000 ng·h/mL. Two close relationships were observed between AUC0–12 and the C3 for infusion and between AUC0–12 and the C8 for oral administration. None of the patients had grades 3–4 aGVHD or other serious complications. What is new and Conclusion: This strategy was well tolerated, and the C3 for twice‐daily infusion and the C8 for oral administration were the optimal points for monitoring of CyA concentration in the early phase of transplantation.