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Combined immunosuppressive therapy with low dose FK506 and antimetabolites in rat allogeneic heart transplantation

Tanabe, M and Todo, S and Murase, N and Irish, W and Miyazawa, H and Fujisaki, S and Starzl, TE (1994) Combined immunosuppressive therapy with low dose FK506 and antimetabolites in rat allogeneic heart transplantation. Transplantation, 58 (1). 23 - 27. ISSN 0041-1337

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Abstract

Following rat heterotopic heart allotransplantation, low to lethal doses of the antimetabolites mizoribine (MIZ), RS-61443 (RS), and AZA were given alone or in combination with subtherapeutic doses of FK506 (0.04 mg/kg/day) for 14 days after transplantation. With the median effect analysis of Chou and Kahan for quantitative drug interactions, substantial therapeutic synergism was demonstrated between FK506 and nontoxic doses of MĪZ (2.5, 5, and 10 mg/kg/day) or AZA (5, 30, and 45 mg/kg/day), which was particularly evident with the lowest dose MIZ (2.5 mg/kg/day). When FK506 was used in combination with MIZ or AZA but not with RS, the maximum effect (peak median graft survival) was enhanced significantly from 15 days (MIZ alone) to 26 days (P < 0.05), and from 19 days (AZA alone) to 32 days (P < 0.0l). In contrast, RS interacted with FK506 no more than additively. Although RS was the most powerful single antimetabolite, the best overall survival was obtained by combining AZA and FK506. The addition of FK506 did not significantly increase the percent mortality and LD < inf > 50 < /inf > of the antimetabolites. © 1994 by Williams and Wilkins.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tanabe, M
Todo, S
Murase, N
Irish, W
Miyazawa, H
Fujisaki, S
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1994
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 58
Number: 1
Page Range: 23 - 27
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062125616, Starzl CV No. 1645
Date Deposited: 08 Apr 2010 17:28
Last Modified: 30 Oct 2017 23:56
URI: http://d-scholarship.pitt.edu/id/eprint/5031

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