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Constitutive and acquired resistance to calcineurin inhibitors in renal transplantation: role of P-glycoprotein-170

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UNSPECIFIED (2000) Constitutive and acquired resistance to calcineurin inhibitors in renal transplantation: role of P-glycoprotein-170. TRANSPLANT INTERNATIONAL, 13 (4). pp. 276-284. ISSN 0934-0874

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Abstract

The present study examines whether resistance to Cyclosporin A (CyA) and Tacrolimus (FK506) develops in Tcells from individual patients and the role of P-glycoprotein 170 (P-gp) in mediating drug resistance. IC(50)s were established for CyA and FK506 in cell cultures from 46 renal allograft recipients. P-gp expression and functional activity were determined by flow cytometry. Mean LD,, for CyA was 29 mu g/li (range 2.5-100) and for FK5061.2 mu g/li (range 0.085-5.5). The sensitivities to the two drugs were correlated (P = 0.0001). There was variation in the ratio of the ID(50)s depending on the drug used for treatment (P = 0.02). There was no difference in P-gp expression and functional activity in patients with sensitive or resistant cells. The data indicate an association between the sensitivities to CyA and FK506 and evidence of selective resistance to whichever drug was used. P-gp drug transport does not explain this variation.

Item Type: Journal Article
Subjects: R Medicine > RD Surgery
Journal or Publication Title: TRANSPLANT INTERNATIONAL
Publisher: SPRINGER-VERLAG
ISSN: 0934-0874
Date: July 2000
Volume: 13
Number: 4
Number of Pages: 9
Page Range: pp. 276-284
Publication Status: Published
URI: http://wrap.warwick.ac.uk/id/eprint/13128

Data sourced from Thomson Reuters' Web of Knowledge

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