Tacrolimus pharmacokinetics in BMT patients.

Abstract:

:The pharmacokinetics of tacrolimus following its administration as monotherapy or in combination with corticosteroids or methotrexate to 31 BMT patients are presented. All patients received i.v. tacrolimus initially and were subsequently switched to p.o. dosing. Patients received methotrexate by i.v. bolus on post-transplantation days 1, 3, 6 and 11. Patients were started on i.v. corticosteroids beginning on post-transplantation day 7. The noncompartmental pharmacokinetics of tacrolimus based on whole blood concentrations were determined following the i.v. and p.o. doses and were not different at steady-state compared to a single dose. The mean terminal elimination half-life of tacrolimus was 18.2 h following i.v. administration; the total body clearance was 71 ml/h/kg, the volume of distribution was 1.67 1/kg. Co-administration of methylprednisolone or methotrexate did not significantly alter tacrolimus pharmacokinetics. The p.o. bioavailability was 31-49%. Trough blood concentrations (Cmin) at 0 h (pre-dose) and 12 h (post-dose) correlated well to AUC(0-12)indicating that, as in solid organ transplantation, Cmin was a good index of drug exposure. Correlation at 0 h (r = 0.92) and at 12 h (r = 0.93) indicate that either time point can be used for therapeutic drug monitoring in patient management.

journal_name

Bone Marrow Transplant

authors

Boswell GW,Bekersky I,Fay J,Wingard J,Antin J,Weisdorf D,Maher R,Fitzsimmons W,Nash R

doi

10.1038/sj.bmt.1701054

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

23-8

issue

1

eissn

0268-3369

issn

1476-5365

journal_volume

21

pub_type

临床试验,杂志文章,随机对照试验
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    doi:

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    更新日期:1996-12-01 00:00:00

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    doi:

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    doi:

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    pub_type: 杂志文章

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    authors: Imahashi N,Suzuki R,Fukuda T,Kakihana K,Kanamori H,Eto T,Mori T,Kobayashi N,Iwato K,Sakura T,Ikegame K,Kurokawa M,Kondo T,Iida H,Sakamaki H,Tanaka J,Kawa K,Morishima Y,Atsuta Y,Miyamura K

    更新日期:2013-01-01 00:00:00

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    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:

    authors: Gardner SF,Lazarus HM,Bednarczyk EM,Creger RJ,Miraldi FD,Leisure G,Green JA

    更新日期:1993-08-01 00:00:00

  • Rapid and sustained hematopoietic reconstitution by peripheral blood stem cell infusion alone following high-dose chemotherapy.

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    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:

    authors: Schwartzberg L,Birch R,Blanco R,Wittlin F,Muscato J,Tauer K,Hazelton B,West W

    更新日期:1993-05-01 00:00:00